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Sample records for ras design simulation

  1. Design and Performance of McRas in SCMs and GEOS I/II GCMs

    NASA Technical Reports Server (NTRS)

    Sud, Yogesh C.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    The design of a prognostic cloud scheme named McRAS (Microphysics of clouds with Relaxed Arakawa-Schubert Scheme) for general circulation models (GCMs) will be discussed. McRAS distinguishes three types of clouds: (1) convective, (2) stratiform, and (3) boundary-layer types. The convective clouds transform and merge into stratiform clouds on an hourly time-scale, while the boundary-layer clouds merge into the stratiform clouds instantly. The cloud condensate converts into precipitation following the auto-conversion equations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, as well as diffuse both horizontally and vertically with a fully interactive cloud-microphysics throughout the life-cycle of the cloud, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry. An evaluation of McRAS in a single column model (SCM) with the GATE Phase III and 5-ARN CART datasets has shown that together with the rest of the model physics, McRAS can simulate the observed temperature, humidity, and precipitation without many systematic errors. The time history and time mean incloud water and ice distribution, fractional cloudiness, cloud optical thickness, origin of precipitation in the convective anvil and towers, and the convective updraft and downdraft velocities and mass fluxes all show a realistic behavior. Performance of McRAS in GEOS 11 GCM shows several satisfactory features but some of the remaining deficiencies suggest need for additional research involving convective triggers and inhibitors, provision for continuously detraining updraft, a realistic scheme for cumulus gravity wave drag, and refinements to physical conditions for ascertaining cloud detrainment level.

  2. Rational design of small molecule inhibitors targeting the Ras GEF, SOS1

    PubMed Central

    Evelyn, Chris R.; Duan, Xin; Biesiada, Jacek; Seibel, William L.; Meller, Jaroslaw; Zheng, Yi

    2014-01-01

    Summary Ras GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine-nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, is found to bind to SOS1, competitively suppresses SOS1-Ras interaction, and dose-dependently inhibits SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity. PMID:25455859

  3. Terahertz Gyrotrons at IAP RAS: Status and New Designs

    NASA Astrophysics Data System (ADS)

    Bratman, V. L.; Glyavin, M. Yu.; Kalynov, Yu. K.; Litvak, A. G.; Luchinin, A. G.; Savilov, A. V.; Zapevalov, V. E.

    2011-03-01

    Powerful gyrotrons with radiation frequencies in the range 0.33-0.65 THz were demonstrated at the IAP as early as in the 1970-1980s. This trend has recently been renewed in connection with a significant increase in interest in terahertz frequency range. In the course of new experiments, the radiation frequency of pulsed gyrotrons was increased up to 1.3 THz and 1 THz at the fundamental and third cyclotron harmonics, respectively. In addition, gyrotrons operated in CW regime with a frequency of 0.3 THz for technological applications (in collaboration with the University of Fukui, Japan) and 0.26 THz for the dynamic nuclear polarization at a high-field NMR were implemented. Designs of a pulsed fundamental-harmonic gyrotron with MW-level power at 0.3 THz and a CW kW-level third-harmonic gyrotron with a frequency of 0.4 THz are currently developed. Estimates show that modern techniques for the creation of strong magnetic fields now make it possible to realize gyrotrons with an operating frequency at least up to 1-1.5 THz. Such generators utilize a relatively low particle energy and can provide higher average power than the existing FELs.

  4. RAS and LES Simulation of the supercritical flow over the waving bed

    NASA Astrophysics Data System (ADS)

    Fu, X.; Ma, H.; Heyman, J.; Mettra, F.; Liu, D.; Ancey, C.

    2013-12-01

    The phenomena of bed forms exist widely in the natural rivers and are still not fully understood. The detailed sediment dynamics near the bed is essential for this problem. However, the fluid dynamics near the bed, which drives the sediment motion, is not clear. In this talk, we focus on the fluid dynamics of supercritical flow over a sinusoidal wavy bed, especially around the wall region. This setup mimics anti-dunes morphology i.e. bedforms that are commonly found in steep mountain streams. In this case, the flow depth and the bedform amplitude have the same order of magnitude with the amplitude of the bedform. To study the detailed fluid flow, a 3-Dimensional numerical simulation of Navier-Stokes equations is performed. Two different models, Reynolds Average Simulation (RAS) and Large Eddy Simulation (LES), are used for the turbulence closure. The two models are validated with experiments carried out on a wavy bed. Particular attention is paid to the fluid shear stress on the wavy bed and the bedform equivalent roughness. LES shows more abilities for this problem. In future, various wavelength and amplitude of the sinus wave will be implemented so that new shear stress formulas and parameterization for the anti-dune roughness in shallow water equations will be proposed.

  5. Designing Simulation Systems

    ERIC Educational Resources Information Center

    Twelker, Paul A.

    1969-01-01

    "The purpose of this paper is to outline the approach to designing instructional simulation systems developed at Teaching Research. The 13 phases of simulation design will be summarized, and an effort will be made to expose the vital decision points that confront the designer as he develops simulation experiences. (Author)

  6. Ras history

    PubMed Central

    2010-01-01

    Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an intensive research effort to understand Ras protein structure, biochemistry and biology. While the ultimate goal has been developing anti-Ras drugs for cancer treatment, discoveries from Ras have laid the foundation for three broad areas of science. First, they focused studies on the origins of cancer to the molecular level, with the subsequent discovery of genes mutated in cancer that now number in the thousands. Second, elucidation of the biochemical mechanisms by which Ras facilitates signal transduction established many of our fundamental concepts of how a normal cell orchestrates responses to extracellular cues. Third, Ras proteins are also founding members of a large superfamily of small GTPases that regulate all key cellular processes and established the versatile role of small GTP-binding proteins in biology. We highlight some of the key findings of the last 28 years. PMID:21686117

  7. Perceptually Augmented Simulator Design.

    PubMed

    Edmunds, T; Pai, D K

    2012-01-01

    Training simulators have proven their worth in a variety of fields, from piloting to air-traffic control to nuclear power station monitoring. Designing surgical simulators, however, poses the challenge of creating trainers that effectively instill not only high-level understanding of the steps to be taken in a given situation, but also the low-level "muscle-memory" needed to perform delicate surgical procedures. It is often impossible to build an ideal simulator that perfectly mimics the haptic experience of a surgical procedure, but by focussing on the aspects of the experience that are perceptually salient we can build simulators that effectively instill learning. We propose a general method for the design of surgical simulators that augment the perceptually salient aspects of an interaction. Using this method, we can increase skill-transfer rates without requiring expensive improvements in the capability of the rendering hardware or the computational complexity of the simulation. In this paper, we present our decomposition-based method for surgical simulator design, and describe a user-study comparing the training effectiveness of a haptic-search-task simulator designed using our method versus an unaugmented simulator. The results show that perception-based task decomposition can be used to improve the design of surgical simulators that effectively impart skill by targeting perceptually significant aspects of the interaction. PMID:26963831

  8. Design, dimensioning, and performance of a research facility for studies on the requirements of fish in RAS environments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recirculating aquaculture systems (RAS) are increasingly being used for Atlantic salmon smolt production. However, knowledge of how the RAS environment affects welfare and performance of Atlantic salmon is limited. For instance, safe limits for chronic exposure to typical compounds in RAS, such as N...

  9. RAS diseases in children

    PubMed Central

    Niemeyer, Charlotte M.

    2014-01-01

    RAS genes encode a family of 21 kDa proteins that are an essential hub for a number of survival, proliferation, differentiation and senescence pathways. Signaling of the RAS-GTPases through the RAF-MEK-ERK pathway, the first identified mitogen-associated protein kinase (MAPK) cascade is essential in development. A group of genetic syndromes, named “RASopathies”, had been identified which are caused by heterozygosity for germline mutations in genes that encode protein components of the RAS/MAPK pathway. Several of these clinically overlapping disorders, including Noonan syndrome, Noonan-like CBL syndrome, Costello syndrome, cardio-facio-cutaneous (CFC) syndrome, neurofibromatosis type I, and Legius syndrome, predispose to cancer and abnormal myelopoiesis in infancy. This review focuses on juvenile myelomonocytic leukemia (JMML), a malignancy of early childhood characterized by initiating germline and/or somatic mutations in five genes of the RAS/MAPK pathway: PTPN11, CBL, NF-1, KRAS and NRAS. Natural courses of these five subtypes differ, although hematopoietic stem cell transplantation remains the only curative therapy option for most children with JMML. With whole-exome sequencing studies revealing few secondary lesions it will be crucial to better understand the RAS/MAPK signaling network with its crosstalks and feed-back loops to carefully design early clinical trials with novel pharmacological agents in this still puzzling leukemia. PMID:25420281

  10. Rational design of point mutation-selective antisense DNA targeted to codon 12 of Ha-ras mRNA in human cells.

    PubMed Central

    Duroux, I; Godard, G; Boidot-Forget, M; Schwab, G; Hélène, C; Saison-Behmoaras, T

    1995-01-01

    Antisense oligodeoxynucleotides targeted to Ha-ras mRNA have been designed to discriminate between the codon 12-mutated oncogene and the normal proto-oncogene. An in vitro assay using two different sources of RNase H (rabbit reticulocyte lysates and nuclear extract from HeLa cells) was used to characterize oligonucleotide binding to normal and mutated Ha-ras mRNA. Short oligonucleotides (12- or 13mers) centered on the mutation had a very high discriminatory efficiency. Longer oligonucleotides (16mers) did not discriminate efficiently between the mutated and the normal mRNA. We have tested the efficacy of dodecanucleotides to induce RNase H cleavage of the full-length mRNA, moving the target sequence from the loop to the stem region which is formed in the vicinity of mutated codon 12. The most selective oligonucleotides were centered on the mutation which is located near the junction between the loop and stem regions even though they were less efficient at inducing RNase H cleavage than those targeted to the loop region. The 12mer antisense oligonucleotide with the highest discriminatory power was selected for cell culture studies. This oligonucleotide inhibited the proliferation of a human cell line which had been transformed with the mutated Ha-ras gene (HBL100ras1) but had no effect on the parental cell line which was transfected with the vector DNA (HBL 100neo) and expressed only the normal Ha-ras gene. Growth inhibition of HBL100ras1 cells was associated with specific ablation of targeted Ha-ras mRNA as shown by RT-PCR. These results show that 'in vitro' evaluation using an RNase H assay allowed us to select an antisense oligonucleotide which elicited a selectivity towards point-mutated Ha-ras mRNA when added at 10 microM concentration to the culture medium of cells expressing wild type and mutated Ha-ras mRNA. Images PMID:7567450

  11. RAS Laboratory Groups

    Cancer.gov

    The RAS Initiative uses multiple technologies to attack RAS-driven cancers. The resources of the Frederick National Lab allocated to the RAS Hub are organized into seven laboratory groups, each contributing to the collaborative effort.

  12. The RAS Initiative

    Cancer.gov

    NCI established the RAS Initiative to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers.

  13. Design, Evaluation and GCM-Performance of a New Parameterization for Microphysics of Clouds with Relaxed Arakawa-Schubert Scheme (McRas)

    NASA Technical Reports Server (NTRS)

    Sud, Y. C.; Walker, G. K.

    1998-01-01

    A prognostic cloud scheme named McRAS (Microphysics of clouds with Relaxed Arakawa-Schubert Scheme) was developed with the aim of improving cloud-microphysics, and cloud-radiation interactions in GCMs. McRAS distinguishes convective, stratiform, and boundary-layer clouds. The convective clouds merge into stratiform clouds on an hourly time-scale, while the boundary-layer clouds do so instantly. The cloud condensate transforms into precipitation following the auto-conversion relations of Sundqvist that contain a parametric adaptation for the Bergeron-Findeisen process of ice crystal growth and collection of cloud condensate by precipitation. All clouds convect, advect, and diffuse both horizontally and vertically with a fully active cloud-microphysics throughout its life-cycle, while the optical properties of clouds are derived from the statistical distribution of hydrometeors and idealized cloud geometry. An evaluation of McRAS in a single column model (SCM) with the GATE Phase III data has shown that McRAS can simulate the observed temperature, humidity, and precipitation without discernible systematic errors. An evaluation with the ARM-CART SCM data in a cloud model intercomparison exercise shows reasonable but not an outstanding accurate simulation. Such a discrepancy is common to almost all models and is related, in part, to the input data quality. McRAS was implemented in the GEOS II GCM. A 50 month integration that was initialized with the ECMWF analysis of observations for January 1, 1987 and forced with the observed sea-surface temperatures and sea-ice distribution and vegetation properties (biomes, and soils), with prognostic soil moisture, snow-cover, and hydrology showed a very realistic simulation of cloud process, incloud water and ice, and cloud-radiative forcing (CRF). The simulated ITCZ showed a realistic time-mean structure and seasonal cycle, while the simulated CRF showed sensitivity to vertical distribution of cloud water which can be easily

  14. Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme*

    PubMed Central

    Evelyn, Chris R.; Biesiada, Jacek; Duan, Xin; Tang, Hong; Shang, Xun; Papoian, Ruben; Seibel, William L.; Nelson, Sandra; Meller, Jaroslaw; Zheng, Yi

    2015-01-01

    The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions. PMID:25825487

  15. Backbone conformational flexibility of the lipid modified membrane anchor of the human N-Ras protein investigated by solid-state NMR and molecular dynamics simulation.

    PubMed

    Vogel, Alexander; Reuther, Guido; Roark, Matthew B; Tan, Kui-Thong; Waldmann, Herbert; Feller, Scott E; Huster, Daniel

    2010-02-01

    The lipid modified human N-Ras protein, implicated in human cancer development, is of particular interest due to its membrane anchor that determines the activity and subcellular location of the protein. Previous solid-state NMR investigations indicated that this membrane anchor is highly dynamic, which may be indicative of backbone conformational flexibility. This article aims to address if a dynamic exchange between three structural models exist that had been determined previously. We applied a combination of solid-state nuclear magnetic resonance (NMR) methods and replica exchange molecular dynamics (MD) simulations using a Ras peptide that represents the terminal seven amino acids of the human N-Ras protein. Analysis of correlations between the conformations of individual amino acids revealed that Cys 181 and Met 182 undergo collective conformational exchange. Two major structures constituting about 60% of all conformations could be identified. The two conformations found in the simulation are in rapid exchange, which gives rise to low backbone order parameters and nuclear spin relaxation as measured by experimental NMR methods. These parameters were also determined from two 300 ns conventional MD simulations, providing very good agreement with the experimental data. PMID:19819220

  16. Hydro/Engineering Geophysical Parameters and Design Response Spectrum for Sustainable Development in Ras Muhammed National Park, Sinai

    NASA Astrophysics Data System (ADS)

    Khalil, Mohamed H.; Gamal, Mohamed A.

    2016-01-01

    The Egyptian government is preparing a sustainable development master plan for the Ras Muhammed National Park (RMNP), south Sinai. Noteworthy, the scarcity of the freshwater resources and close proximity to the active seismic zones of the Gulf of Aqaba implicate geophysical investigations for the fresh groundwater aquifers and construct a design response spectrum, respectively. Accordingly, 14 VESs, hydro/engineering geophysical analysis, pumping tests, downhole seismic test, a design response spectrum for buildings, and borehole data were carried out in the study area. The unconfined freshwater aquifer was effectively depicted with true resistivities, thickness, and EC ranged from 56 to 135 Ω m, 11 to 112 m, and 1.4 to 7.1 mS/m, respectively. The Northeastern part was characterized by higher aquifer potentiality, where coarser grains size, highest thickness (112 m), high true resistivity (135 Ω m), groundwater flow (0.074 m3/day), tortuosity (1.293-1.312), formation resistivity factor (4.1-4.6), and storativity (0.281-0.276). An increase in pumping rate was accompanied by an increase in well loss, increase in aquifer losses, decrease in well specific capacity, and decrease in well efficiency. Design response spectrum prognosticated the short buildings (<7 floors) in RMNP to be suffering from a high peak horizontal acceleration and shear forces for acceleration between 0.25 and 0.35 g. Therefore, appropriate detailing of shear reinforcement is indispensable to reduce the risk of structural damages at RMNP.

  17. Hydro/Engineering Geophysical Parameters and Design Response Spectrum for Sustainable Development in Ras Muhammed National Park, Sinai

    NASA Astrophysics Data System (ADS)

    Khalil, Mohamed H.; Gamal, Mohamed A.

    2016-06-01

    The Egyptian government is preparing a sustainable development master plan for the Ras Muhammed National Park (RMNP), south Sinai. Noteworthy, the scarcity of the freshwater resources and close proximity to the active seismic zones of the Gulf of Aqaba implicate geophysical investigations for the fresh groundwater aquifers and construct a design response spectrum, respectively. Accordingly, 14 VESs, hydro/engineering geophysical analysis, pumping tests, downhole seismic test, a design response spectrum for buildings, and borehole data were carried out in the study area. The unconfined freshwater aquifer was effectively depicted with true resistivities, thickness, and EC ranged from 56 to 135 Ω m, 11 to 112 m, and 1.4 to 7.1 mS/m, respectively. The Northeastern part was characterized by higher aquifer potentiality, where coarser grains size, highest thickness (112 m), high true resistivity (135 Ω m), groundwater flow (0.074 m3/day), tortuosity (1.293-1.312), formation resistivity factor (4.1-4.6), and storativity (0.281-0.276). An increase in pumping rate was accompanied by an increase in well loss, increase in aquifer losses, decrease in well specific capacity, and decrease in well efficiency. Design response spectrum prognosticated the short buildings (<7 floors) in RMNP to be suffering from a high peak horizontal acceleration and shear forces for acceleration between 0.25 and 0.35 g. Therefore, appropriate detailing of shear reinforcement is indispensable to reduce the risk of structural damages at RMNP.

  18. SUMO wrestling with Ras

    PubMed Central

    Zhang, Haibo; Luo, Ji

    2016-01-01

    ABSTRACT This review discusses our current understanding of the small ubiquitin-like modifier (SUMO) pathway and how it functionally intersects with Ras signaling in cancer. The Ras family of small GTPases are frequently mutated in cancer. The role of the SUMO pathway in cancer and in Ras signaling is currently not well understood. Recent studies have shown that the SUMO pathway can both regulate Ras/MAPK pathway activity directly and support Ras-driven oncogenesis through the regulation of proteins that are not direct Ras effectors. We recently discovered that in Ras mutant cancer cells, the SUMOylation status of a subset of proteins is altered and one such protein, KAP1, is required for Ras-driven transformation. A better understanding of the functional interaction between the SUMO and Ras pathways could lead to new insights into the mechanism of Ras-driven oncogenesis. PMID:27057691

  19. Inhibitors of Ras-SOS Interactions.

    PubMed

    Lu, Shaoyong; Jang, Hyunbum; Zhang, Jian; Nussinov, Ruth

    2016-04-19

    Activating Ras mutations are found in about 30 % of human cancers. Ras activation is regulated by guanine nucleotide exchange factors, such as the son of sevenless (SOS), which form protein-protein interactions (PPIs) with Ras and catalyze the exchange of GDP by GTP. This is the rate-limiting step in Ras activation. However, Ras surfaces lack any evident suitable pockets where a molecule might bind tightly, rendering Ras proteins still 'undruggable' for over 30 years. Among the alternative approaches is the design of inhibitors that target the Ras-SOS PPI interface, a strategy that is gaining increasing recognition for treating Ras mutant cancers. Herein we focus on data that has accumulated over the past few years pertaining to the design of small-molecule modulators or peptide mimetics aimed at the interface of the Ras-SOS PPI. We emphasize, however, that even if such Ras-SOS therapeutics are potent, drug resistance may emerge. To counteract this development, we propose "pathway drug cocktails", that is, drug combinations aimed at parallel (or compensatory) pathways. A repertoire of classified cancer, cell/tissue, and pathway/protein combinations would be beneficial toward this goal. PMID:26630662

  20. Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP.

    PubMed

    Garcia, Lia C; Donadío, Lucia Gandolfi; Mann, Ella; Kolusheva, Sofiya; Kedei, Noemi; Lewin, Nancy E; Hill, Colin S; Kelsey, Jessica S; Yang, Jing; Esch, Timothy E; Santos, Marina; Peach, Megan L; Kelley, James A; Blumberg, Peter M; Jelinek, Raz; Marquez, Victor E; Comin, Maria J

    2014-06-15

    The development of selective agents capable of discriminating between protein kinase C (PKC) isoforms and other diacylglycerol (DAG)-responsive C1 domain-containing proteins represents an important challenge. Recent studies have highlighted the role that Ras guanine nucleotide-releasing protein (RasGRP) isoforms play both in immune responses as well as in the development of prostate cancer and melanoma, suggesting that the discovery of selective ligands could have potential therapeutic value. Thus far, the N-methyl-substituted indololactone 1 is the agonist with the highest reported potency and selectivity for RasGRP relative to PKC. Here we present the synthesis, binding studies, cellular assays and biophysical analysis of interactions with model membranes of a family of regioisomers of 1 (compounds 2-5) that differ in the position of the linkage between the indole ring and the lactone moiety. These structural variations were studied to explore the interaction of the active complex (C1 domain-ligand) with cellular membranes, which is believed to be an important factor for selectivity in the activation of DAG-responsive C1 domain containing signaling proteins. All compounds were potent and selective activators of RasGRP when compared to PKCα with selectivities ranging from 6 to 65 fold. However, the parent compound 1 was appreciably more selective than any of the other isomers. In intact cells, modest differences in the patterns of translocation of the C1 domain targets were observed. Biophysical studies using giant vesicles as model membranes did show substantial differences in terms of molecular interactions impacting lipid organization, dynamics and membrane insertion. However, these differences did not yield correspondingly large changes in patterns of biological response, at least for the parameters examined. PMID:24794745

  1. Synthesis, Biological, and Biophysical Studies of DAG-indololactones Designed as Selective Activators of RasGRP

    PubMed Central

    Garcia, Lia C.; Donadío, Lucia Gandolfi; Mann, Ella; Kolusheva, Sofiya; Kedei, Noemi; Lewin, Nancy E.; Hill, Colin S.; Kelsey, Jessica S.; Yang, Jing; Esch, Timothy E.; Santos, Marina; Peach, Megan L.; Kelley, James A.; Blumberg, Peter M.; Jelinek, Raz; Marquez, Victor E.; Comin, Maria J.

    2014-01-01

    The development of selective agents capable of discriminating between protein kinase C (PKC) isoforms and other diacylglycerol (DAG)-responsive C1 domain-containing proteins represents an important challenge. Recent studies have highlighted the role that Ras guanine nucleotide-releasing protein (RasGRP) isoforms play both in immune responses as well as in the development of prostate cancer and melanoma, suggesting that the discovery of selective ligands could have potential therapeutic value. Thus far, the N-methyl-substituted indololactone 1 is the agonist with the highest reported potency and selectivity for RasGRP relative to PKC. Here we present the synthesis, binding studies, cellular assays and biophysical analysis of interactions with model membranes of a family of regioisomers of 1 (compounds 2 to 5) that differ in the position of the linkage between the indole ring and the lactone moiety. These structural variations were studied to explore the interaction of the active complex (C1 domain-ligand) with cellular membranes, which is believed to be an important factor for selectivity in the activation of DAG-responsive C1 domain containing signaling proteins. All compounds were potent and selective activators of RasGRP when compared to PKCα with selectivities ranging from 6 to 65 fold. However, the parent compound 1 was appreciably more selective than any of the other isomers. In intact cells, modest differences in the patterns of translocation of the C1 domain targets were observed. Biophysical studies using giant vesicles as model membranes did show substantial differences in terms of molecular interactions impacting lipid organization, dynamics and membrane insertion. However, these differences did not yield correspondingly large changes in patterns of biological response, at least for the parameters examined. PMID:24794745

  2. A channel simulator design study

    NASA Technical Reports Server (NTRS)

    Devito, D. M.; Goutmann, M. M.; Harper, R. C.

    1971-01-01

    A propagation path simulator was designed for the channel between a Tracking and Data Relay Satellite in geostationary orbit and a user spacecraft orbiting the earth at an altitude between 200 and 4000 kilometers. The simulator is required to duplicate the time varying parameters of the propagation channel.

  3. LSST: Cadence Design and Simulation

    NASA Astrophysics Data System (ADS)

    Cook, Kem H.; Pinto, P. A.; Delgado, F.; Miller, M.; Petry, C.; Saha, A.; Gee, P. A.; Tyson, J. A.; Ivezic, Z.; Jones, L.; LSST Collaboration

    2009-01-01

    The LSST Project has developed an operations simulator to investigate how best to observe the sky to achieve its multiple science goals. The simulator has a sophisticated model of the telescope and dome to properly constrain potential observing cadences. This model has also proven useful for investigating various engineering issues ranging from sizing of slew motors, to design of cryogen lines to the camera. The simulator is capable of balancing cadence goals from multiple science programs, and attempts to minimize time spent slewing as it carries out these goals. The operations simulator has been used to demonstrate a 'universal' cadence which delivers the science requirements for a deep cosmology survey, a Near Earth Object Survey and good sampling in the time domain. We will present the results of simulating 10 years of LSST operations using realistic seeing distributions, historical weather data, scheduled engineering downtime and current telescope and camera parameters. These simulations demonstrate the capability of the LSST to deliver a 25,000 square degree survey probing the time domain including 20,000 square degrees for a uniform deep, wide, fast survey, while effectively surveying for NEOs over the same area. We will also present our plans for future development of the simulator--better global minimization of slew time and eventual transition to a scheduler for the real LSST.

  4. Spinning Rocket Simulator Turntable Design

    NASA Technical Reports Server (NTRS)

    Miles, Robert W.

    2001-01-01

    Contained herein is the research and data acquired from the Turntable Design portion of the Spinning Rocket Simulator (SRS) project. The SRS Project studies and eliminates the effect of coning on thrust-propelled spacecraft. This design and construction of the turntable adds a structural support for the SRS model and two degrees of freedom. The two degrees of freedom, radial and circumferential, will help develop a simulated thrust force perpendicular to the plane of the spacecraft model while undergoing an unstable coning motion. The Turntable consists of a ten-foot linear track mounted to a sprocket and press-fit to a thrust bearing. A two-inch high column grounded by a Triangular Baseplate supports this bearing and houses the slip rings and pressurized, air-line swivel. The thrust bearing allows the entire system to rotate under the moment applied through the chain-driven sprocket producing a circumferential degree of freedom. The radial degree of freedom is given to the model through the helically threaded linear track. This track allows the Model Support and Counter Balance to simultaneously reposition according to the coning motion of the Model. Two design factors that hinder the linear track are bending and twist due to torsion. A Standard Aluminum "C" channel significantly reduces these two deflections. Safety considerations dictate the design of all the components involved in this project.

  5. RAS Ordinary Meeting

    NASA Astrophysics Data System (ADS)

    2014-08-01

    Here are summarized talks from the February and March RAS Ordinary Meetings. The February meeting also enjoyed the Eddington Lecture from Prof. Lisa Kewley (Australian National University) on galaxy evolution in 3D.

  6. The RAS Problem

    Cancer.gov

    More than 30% of all human cancers, including a high percentage of lung and colon cancers and 95% of pancreatic cancers are driven by mutations and possibly amplification (increased copies) of RAS genes.

  7. Simulation of a Wall-Bounded Flow using a Hybrid LES/RAS Approach with Turbulence Recycling

    NASA Technical Reports Server (NTRS)

    Quinlan, Jesse R.; Mcdaniel, James; Baurle, Robert A.

    2012-01-01

    Simulations of a supersonic recessed-cavity flow are performed using a hybrid large-eddy/ Reynolds-averaged simulation approach utilizing an inflow turbulence recycling procedure and hybridized inviscid flux scheme. Calorically perfect air enters the three-dimensional domain at a free stream Mach number of 2.92. Simulations are performed to assess grid sensitivity of the solution, efficacy of the turbulence recycling, and effect of the shock sensor used with the hybridized inviscid flux scheme. Analysis of the turbulent boundary layer upstream of the rearward-facing step for each case indicates excellent agreement with theoretical predictions. Mean velocity and pressure results are compared to Reynolds-averaged simulations and experimental data for each case, and these comparisons indicate good agreement on the finest grid. Simulations are repeated on a coarsened grid, and results indicate strong grid density sensitivity. The effect of turbulence recycling on the solution is illustrated by performing coarse grid simulations with and without inflow turbulence recycling. Two shock sensors, one of Ducros and one of Larsson, are assessed for use with the hybridized inviscid flux reconstruction scheme.

  8. Xyce parallel electronic simulator design.

    SciTech Connect

    Thornquist, Heidi K.; Rankin, Eric Lamont; Mei, Ting; Schiek, Richard Louis; Keiter, Eric Richard; Russo, Thomas V.

    2010-09-01

    This document is the Xyce Circuit Simulator developer guide. Xyce has been designed from the 'ground up' to be a SPICE-compatible, distributed memory parallel circuit simulator. While it is in many respects a research code, Xyce is intended to be a production simulator. As such, having software quality engineering (SQE) procedures in place to insure a high level of code quality and robustness are essential. Version control, issue tracking customer support, C++ style guildlines and the Xyce release process are all described. The Xyce Parallel Electronic Simulator has been under development at Sandia since 1999. Historically, Xyce has mostly been funded by ASC, the original focus of Xyce development has primarily been related to circuits for nuclear weapons. However, this has not been the only focus and it is expected that the project will diversify. Like many ASC projects, Xyce is a group development effort, which involves a number of researchers, engineers, scientists, mathmaticians and computer scientists. In addition to diversity of background, it is to be expected on long term projects for there to be a certain amount of staff turnover, as people move on to different projects. As a result, it is very important that the project maintain high software quality standards. The point of this document is to formally document a number of the software quality practices followed by the Xyce team in one place. Also, it is hoped that this document will be a good source of information for new developers.

  9. Sensitivity of Cirrus and Mixed-phase Clouds to the Ice Nuclei Spectra in McRAS-AC: Single Column Model Simulations

    NASA Technical Reports Server (NTRS)

    Betancourt, R. Morales; Lee, D.; Oreopoulos, L.; Sud, Y. C.; Barahona, D.; Nenes, A.

    2012-01-01

    The salient features of mixed-phase and ice clouds in a GCM cloud scheme are examined using the ice formation parameterizations of Liu and Penner (LP) and Barahona and Nenes (BN). The performance of LP and BN ice nucleation parameterizations were assessed in the GEOS-5 AGCM using the McRAS-AC cloud microphysics framework in single column mode. Four dimensional assimilated data from the intensive observation period of ARM TWP-ICE campaign was used to drive the fluxes and lateral forcing. Simulation experiments where established to test the impact of each parameterization in the resulting cloud fields. Three commonly used IN spectra were utilized in the BN parameterization to described the availability of IN for heterogeneous ice nucleation. The results show large similarities in the cirrus cloud regime between all the schemes tested, in which ice crystal concentrations were within a factor of 10 regardless of the parameterization used. In mixed-phase clouds there are some persistent differences in cloud particle number concentration and size, as well as in cloud fraction, ice water mixing ratio, and ice water path. Contact freezing in the simulated mixed-phase clouds contributed to transfer liquid to ice efficiently, so that on average, the clouds were fully glaciated at T approximately 260K, irrespective of the ice nucleation parameterization used. Comparison of simulated ice water path to available satellite derived observations were also performed, finding that all the schemes tested with the BN parameterization predicted 20 average values of IWP within plus or minus 15% of the observations.

  10. Fully conservative coupling of HEC-1 RAS with MODFLOW to simulate stream-aquifer interactions in a drainage basin 1960

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This work describes the application of a methodology designed to improve the representation of water surface profiles along open drain channels within the framework of regional groundwater modeling. The proposed methodology employs an iterative procedure that combines two public domain computational...

  11. RasGRP Ras guanine nucleotide exchange factors in cancer

    PubMed Central

    Ksionda, Olga; Limnander, Andre

    2014-01-01

    Summary RasGRP proteins are activators of Ras and other related small GTPases by the virtue of functioning as guanine nucleotide exchange factors (GEFs). In vertebrates, four RasGRP family members have been described. RasGRP-1 through −4 share many structural domains but there are also subtle differences between each of the different family members. Whereas SOS RasGEFs are ubiquitously expressed, RasGRP proteins are expressed in distinct patterns, such as in different cells of the hematopoietic system and in the brain. Most studies have concentrated on the role of RasGRP proteins in the development and function of immune cell types because of the predominant RasGRP expression profiles in these cells and the immune phenotypes of mice deficient for Rasgrp genes. However, more recent studies demonstrate that RasGRPs also play an important role in tumorigenesis. Examples are skin- and hematological-cancers but also solid malignancies such as melanoma or prostate cancer. These novel studies bring up many new and unanswered questions related to the molecular mechanism of RasGRP-driven oncogenesis, such as new receptor systems that RasGRP appears to respond to as well as regulatory mechanism for RasGRP expression that appear to be perturbed in these cancers. Here we will review some of the known aspects of RasGRP biology in lymphocytes and will discuss the exciting new notion that RasGRP Ras exchange factors play a role in oncogenesis downstream of various growth factor receptors. PMID:24744772

  12. Automated Simulation For Analysis And Design

    NASA Technical Reports Server (NTRS)

    Cantwell, E.; Shenk, Tim; Robinson, Peter; Upadhye, R.

    1992-01-01

    Design Assistant Workstation (DAWN) software being developed to facilitate simulation of qualitative and quantitative aspects of behavior of life-support system in spacecraft, chemical-processing plant, heating and cooling system of large building, or any of variety of systems including interacting process streams and processes. Used to analyze alternative design scenarios or specific designs of such systems. Expert system will automate part of design analysis: reason independently by simulating design scenarios and return to designer with overall evaluations and recommendations.

  13. Space shuttle visual simulation system design study

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A recommendation and a specification for the visual simulation system design for the space shuttle mission simulator are presented. A recommended visual system is described which most nearly meets the visual design requirements. The cost analysis of the recommended system covering design, development, manufacturing, and installation is reported. Four alternate systems are analyzed.

  14. Engineering design and integration simulation utilization manual

    NASA Technical Reports Server (NTRS)

    Hirsch, G. N.

    1976-01-01

    A description of the Engineering Design Integration (EDIN) Simulation System as it exists at Johnson Space Center is provided. A discussion of the EDIN Simulation System capabilities and applications is presented.

  15. In service design by simulations

    SciTech Connect

    Nasr H. Ghoniem

    2004-03-14

    Irradiation of materials by energetic particles (e.g. electrons, ions and neutrons) is associated with very high internal power dissipation, which can drive the underlying nano- and microstructure far from normal equilibrium conditions. One of the most unusual responses in this connection is the ability of the material's nano- and microstructure to self-assemble in well-organized, two- and three-dimensional periodic arrangements. We reviewed and assessed experimental evidence and theoretical models pertaining to the physical understanding of nano- and microstructure self-organization under irradiation conditions. Experimental observations on the formation of self-organized defect clusters, dislocation loops, voids and bubbles were presented and critically assessed. Implantation of metals with energetic helium results in remarkable self-assembled bubble super-lattices with wavelengths (super-lattice parameters) in the range of 5-8 nm. Ion and neutron irradiation produce a wide variety of self-assembled 3-D defect walls and void lattices, with wavelengths that can be tailored in the range of 10's to 100's of nanometers. Theoretical models aimed at explaining these observations were introduced, and a consistent description of many features is outlined. The primary focus of the most recent modeling efforts, which are based on stability theory and concepts of non-linear dynamics, was to determine criteria for the evolution and spatial symmetry of self-organized microstructures. The correspondence between this theoretical framework and experimental observations was also examined, highlighting areas of agreement and pointing out unresolved questions. The main objective of this research was to develop new computational tools for in-service design and performance prediction of advanced fusion material systems by computational simulation. We also need to develop these computational tools to assist in planning and assessment of corresponding radiation experiments. In the

  16. Students Design a Depression Simulation.

    ERIC Educational Resources Information Center

    Roessler, Michael

    1987-01-01

    This article describes how an eighth grade class developed a computer-based social studies simulation on the Great Depression. Included are objectives for such development activities, a set of steps for guiding development, a discussion of potential difficulties and rewards, data on student reactions to simulation development, and information on…

  17. Converging Lens Simulation Design and Image Predictions

    ERIC Educational Resources Information Center

    Bryan, J. A.; Slough, S. W.

    2009-01-01

    While computer technology continues to enhance the teaching and learning of all science disciplines, computer simulations, in particular, have become exceptionally beneficial in physics education. In addition to the manner in which physics instructors integrate computer simulations into their instructional practices, the design of a simulation may…

  18. Shuttle mission simulator hardware conceptual design report

    NASA Technical Reports Server (NTRS)

    Burke, J. F.

    1973-01-01

    The detailed shuttle mission simulator hardware requirements are discussed. The conceptual design methods, or existing technology, whereby those requirements will be fulfilled are described. Information of a general nature on the total design problem plus specific details on how these requirements are to be satisfied are reported. The configuration of the simulator is described and the capabilities for various types of training are identified.

  19. Simulation and Spacecraft Design: Engineering Mars Landings.

    PubMed

    Conway, Erik M

    2015-10-01

    A key issue in history of technology that has received little attention is the use of simulation in engineering design. This article explores the use of both mechanical and numerical simulation in the design of the Mars atmospheric entry phases of the Viking and Mars Pathfinder missions to argue that engineers used both kinds of simulation to develop knowledge of their designs' likely behavior in the poorly known environment of Mars. Each kind of simulation could be used as a warrant of the other's fidelity, in an iterative process of knowledge construction. PMID:26593710

  20. [Design of an adjustable simulated lung].

    PubMed

    Xu, Liang; Luo, Zhe

    2011-03-01

    We designed an adjustable simulated lung for clinical use. Depending on the feature of adjustable resistance and compliance, the device could simulate various pathological changes of lung, such as obstructive diseases and restrictive diseases. Thru simulating various pathological conditions with the device, the clinicians could learn how to manipulate a mechanical ventilator. In addition, the device has a leakage equipment for simulating leakage of respiratory circuit, depending on which the clinicians could learn more about ventilators. PMID:21706793

  1. Simulator design for advanced ISDN satellite design and experiments

    NASA Technical Reports Server (NTRS)

    Pepin, Gerald R.

    1992-01-01

    This simulation design task completion report documents the simulation techniques associated with the network models of both the Interim Service ISDN (integrated services digital network) Satellite (ISIS) and the Full Service ISDN Satellite (FSIS) architectures. The ISIS network model design represents satellite systems like the Advanced Communication Technology Satellite (ACTS) orbiting switch. The FSIS architecture, the ultimate aim of this element of the Satellite Communications Applications Research (SCAR) program, moves all control and switching functions on-board the next generation ISDN communication satellite. The technical and operational parameters for the advanced ISDN communications satellite design will be obtained from the simulation of ISIS and FSIS engineering software models for their major subsystems. Discrete events simulation experiments will be performed with these models using various traffic scenarios, design parameters and operational procedures. The data from these simulations will be used to determine the engineering parameters for the advanced ISDN communications satellite.

  2. Simulation of integrated beam experiment designs

    SciTech Connect

    Grote, D.P.; Sharp, W.M.

    2004-06-11

    Simulation of designs of an Integrated Beam Experiment (IBX) class accelerator have been carried out. These simulations are an important tool for validating such designs. Issues such as envelope mismatch and emittance growth can be examined in a self-consistent manner, including the details of injection, accelerator transitions, long-term transport, and longitudinal compression. The simulations are three-dimensional and time-dependent, and begin at the source. They continue up through the end of the acceleration region, at which point the data is passed on to a separate simulation of the drift compression. Results are be presented.

  3. Prosthetic knee design by simulation

    SciTech Connect

    Hollerbach, K; Hollister, A

    1999-07-30

    Although 150,000 total knee replacement surgeries are performed annually in North America, current designs of knee prostheses have mechanical problems that include a limited range of motion, abnormal gait patterns, patellofemoral joint dysfunction, implant loosening or subsidence, and excessive wear. These problems fall into three categories: failure to reproduce normal joint kinematics, which results in altered limb function; bone-implant interface failure; and material failure. Modern computer technology can be used to design, prototype, and test new total knee implants. The design team uses the full range of CAD-CAM to design and produce implant prototypes for mechanical and clinical testing. Closer approximation of natural knee kinematics and kinetics is essential for improved patient function and diminished implant loads. Current knee replacement designs are based on 19th Century theories that the knee moves about a variable axis of rotation. Recent research has shown, however, that knee motion occurs about two fixed, offset axes of rotation. These aces are not perpendicular to the long axes of the bones or to each other, and the axes do not intersect. Bearing surfaces of mechanisms that move about axes of rotation are surfaces of revolution of those axes which advanced CAD technology can produce. Solids with surfaces of revolution for the two axes of rotation for the knee have been made using an HP9000 workstation and Structural Ideas Master Series CAD software at ArthroMotion. The implant's CAD model should closely replicate movements of the normal knee. The knee model will have a range of flexion-extension (FE) from -5 to 120 degrees. Movements include varus, valgus, internal and external rotation, as well as flexion and extension. The patellofemoral joint is aligned perpendicular to the FE axis and replicates the natural joint more closely than those of existing prostheses. The bearing surfaces will be more congruent than current designs and should

  4. Refinery burner simulation design architecture summary.

    SciTech Connect

    Pollock, Guylaine M.; McDonald, Michael James; Halbgewachs, Ronald D.

    2011-10-01

    This report describes the architectural design for a high fidelity simulation of a refinery and refinery burner, including demonstrations of impacts to the refinery if errors occur during the refinery process. The refinery burner model and simulation are a part of the capabilities within the Sandia National Laboratories Virtual Control System Environment (VCSE). Three components comprise the simulation: HMIs developed with commercial SCADA software, a PLC controller, and visualization software. All of these components run on different machines. This design, documented after the simulation development, incorporates aspects not traditionally seen in an architectural design, but that were utilized in this particular demonstration development. Key to the success of this model development and presented in this report are the concepts of the multiple aspects of model design and development that must be considered to capture the necessary model representation fidelity of the physical systems.

  5. Shuttle mission simulator software conceptual design

    NASA Technical Reports Server (NTRS)

    Burke, J. F.

    1973-01-01

    Software conceptual designs (SCD) are presented for meeting the simulator requirements for the shuttle missions. The major areas of the SCD discussed include: malfunction insertion, flight software, applications software, systems software, and computer complex.

  6. Simulation as an Aid to Experimental Design.

    ERIC Educational Resources Information Center

    Frazer, Jack W.; And Others

    1983-01-01

    Discusses simulation program to aid in the design of enzyme kinetic experimentation (includes sample runs). Concentration versus time profiles of any subset or all nine states of reactions can be displayed with/without simulated instrumental noise, allowing the user to estimate the practicality of any proposed experiment given known instrument…

  7. Simulation, Design Abstraction, and SystemC

    ERIC Educational Resources Information Center

    Harcourt, Ed

    2007-01-01

    SystemC is a system-level design and simulation language based on C++. We've been using SystemC for computer organization and design projects for the past several years. Because SystemC is embedded in C++ it contains the powerful abstraction mechanisms of C++ not found in traditional hardware description languages, such as support for…

  8. Computer Simulation For Design Of TWT's

    NASA Technical Reports Server (NTRS)

    Bartos, Karen F.; Fite, E. Brian; Shalkhauser, Kurt A.; Sharp, G. Richard

    1992-01-01

    A three-dimensional finite-element analytical technique facilitates design and fabrication of traveling-wave-tube (TWT) slow-wave structures. Used to perform thermal and mechanical analyses of TWT designed with variety of configurations, geometries, and materials. Using three-dimensional computer analysis, designer able to simulate building and testing of TWT, with consequent substantial saving of time and money. Technique enables detailed look into operation of traveling-wave tubes to help improve performance for future communications systems.

  9. Design and simulation of a gyroklystron amplifier

    SciTech Connect

    Chauhan, M. S. Swati, M. V.; Jain, P. K.

    2015-03-15

    In the present paper, a design methodology of the gyroklystron amplifier has been described and subsequently used for the design of a typically selected 200 kW, Ka-band, four-cavity gyroklystron amplifier. This conceptual device design has been validated through the 3D particle-in-cell (PIC) simulation and nonlinear analysis. Commercially available PIC simulation code “MAGIC” has been used for the electromagnetic study at the different location of the device RF interaction structure for the beam-absent case, i.e., eigenmode study as well as for the electron beam and RF wave interaction behaviour study in the beam present case of the gyroklystron. In addition, a practical problem of misalignment of the RF cavities with drift tubes within the tube has been also investigated and its effect on device performance studied. The analytical and simulation results confirmed the validity of the gyroklystron device design. The PIC simulation results of the present gyroklystron produced a stable RF output power of ∼218 kW for 0% velocity spread at 35 GHz, with ∼45 dB gain, 37% efficiency, and a bandwidth of 0.3% for a 70 kV, 8.2 A gyrating electron beam. The simulated values of RF output power have been found in agreement with the nonlinear analysis results within ∼5%. Further, the PIC simulation has been extended to study a practical problem of misalignment of the cavities axis and drift tube axis of the gyroklystron amplifier and found that the RF output power is more sensitive to misalignments in comparison to the device bandwidth. The present paper, gyroklystron device design, nonlinear analysis, and 3D PIC simulation using commercially available code had been systematically described would be of use to the high-power gyro-amplifier tube designers and research scientists.

  10. Design and simulation of a gyroklystron amplifier

    NASA Astrophysics Data System (ADS)

    Chauhan, M. S.; Swati, M. V.; Jain, P. K.

    2015-03-01

    In the present paper, a design methodology of the gyroklystron amplifier has been described and subsequently used for the design of a typically selected 200 kW, Ka-band, four-cavity gyroklystron amplifier. This conceptual device design has been validated through the 3D particle-in-cell (PIC) simulation and nonlinear analysis. Commercially available PIC simulation code "MAGIC" has been used for the electromagnetic study at the different location of the device RF interaction structure for the beam-absent case, i.e., eigenmode study as well as for the electron beam and RF wave interaction behaviour study in the beam present case of the gyroklystron. In addition, a practical problem of misalignment of the RF cavities with drift tubes within the tube has been also investigated and its effect on device performance studied. The analytical and simulation results confirmed the validity of the gyroklystron device design. The PIC simulation results of the present gyroklystron produced a stable RF output power of ˜218 kW for 0% velocity spread at 35 GHz, with ˜45 dB gain, 37% efficiency, and a bandwidth of 0.3% for a 70 kV, 8.2 A gyrating electron beam. The simulated values of RF output power have been found in agreement with the nonlinear analysis results within ˜5%. Further, the PIC simulation has been extended to study a practical problem of misalignment of the cavities axis and drift tube axis of the gyroklystron amplifier and found that the RF output power is more sensitive to misalignments in comparison to the device bandwidth. The present paper, gyroklystron device design, nonlinear analysis, and 3D PIC simulation using commercially available code had been systematically described would be of use to the high-power gyro-amplifier tube designers and research scientists.

  11. Detector simulation needs for detector designers

    SciTech Connect

    Hanson, G.G.

    1987-11-01

    Computer simulation of the components of SSC detectors and of the complete detectors will be very important for the designs of the detectors. The ratio of events from interesting physics to events from background processes is very low, so detailed understanding of detector response to the backgrounds is needed. Any large detector for the SSC will be very complex and expensive and every effort must be made to design detectors which will have excellent performance and will not have to undergo major rebuilding. Some areas in which computer simulation is particularly needed are pattern recognition in tracking detectors and development of shower simulation code which can be trusted as an aid in the design and optimization of calorimeters, including their electron identification performance. Existing codes require too much computer time to be practical and need to be compared with test beam data at energies of several hundred GeV. Computer simulation of the processing of the data, including electronics response to the signals from the detector components, processing of the data by microprocessors on the detector, the trigger, and data acquisition will be required. In this report we discuss the detector simulation needs for detector designers.

  12. Simulation as an aid to experimental design

    SciTech Connect

    Frazer, J.W.; Balaban, D.J.; Wang, J.L.

    1983-05-01

    A simulator of chemical reactions can aid the scientist in the design of experimentation. They are of great value when studying enzymatic kinetic reactions. One such simulator is a numerical ordinary differential equation solver which uses interactive graphics to provide the user with the capability to simulate an extremely wide range of enzyme reaction conditions for many types of single substrate reactions. The concentration vs. time profiles of any subset or all nine states of a complex reaction can be displayed with and without simulated instrumental noise. Thus the user can estimate the practicality of any proposed experimentation given known instrumental noise. The experimenter can readily determine which state provides the most information related to the proposed kinetic parameters and mechanism. A general discussion of the program including the nondimensionalization of the set of differential equations is included. Finally, several simulation examples are shown and the results discussed.

  13. Design of penicillin fermentation process simulation system

    NASA Astrophysics Data System (ADS)

    Qi, Xiaoyu; Yuan, Zhonghu; Qi, Xiaoxuan; Zhang, Wenqi

    2011-10-01

    Real-time monitoring for batch process attracts increasing attention. It can ensure safety and provide products with consistent quality. The design of simulation system of batch process fault diagnosis is of great significance. In this paper, penicillin fermentation, a typical non-linear, dynamic, multi-stage batch production process, is taken as the research object. A visual human-machine interactive simulation software system based on Windows operation system is developed. The simulation system can provide an effective platform for the research of batch process fault diagnosis.

  14. Memory interface simulator: A computer design aid

    NASA Technical Reports Server (NTRS)

    Taylor, D. S.; Williams, T.; Weatherbee, J. E.

    1972-01-01

    Results are presented of a study conducted with a digital simulation model being used in the design of the Automatically Reconfigurable Modular Multiprocessor System (ARMMS), a candidate computer system for future manned and unmanned space missions. The model simulates the activity involved as instructions are fetched from random access memory for execution in one of the system central processing units. A series of model runs measured instruction execution time under various assumptions pertaining to the CPU's and the interface between the CPU's and RAM. Design tradeoffs are presented in the following areas: Bus widths, CPU microprogram read only memory cycle time, multiple instruction fetch, and instruction mix.

  15. IAA RAS Radio Telescope Monitoring System

    NASA Astrophysics Data System (ADS)

    Mikhailov, A.; Lavrov, A.

    2007-07-01

    Institute of Applied Astronomy of the Russian Academy of Sciences (IAA RAS) has three identical radio telescopes, the receiving complex of which consists of five two-channel receivers of different bands, six cryogen systems, and additional devices: four local oscillators, phase calibration generators and IF commutator. The design, hardware and data communication protocol are described. The most convenient way to join the devices of the receiving complex into the common monitoring system is to use the interface which allows to connect numerous devices to the data bus. For the purpose of data communication regulation and to exclude conflicts, a data communication protocol has been designed, which operates with complex formatted data sequences. Formation of such sequences requires considerable data processing capability. That is provided by a microcontroller chip in each slave device. The test version of the software for the central computer has been developed in IAA RAS. We are developing the Mark IV FS software extension modules, which will allow us to control the receiving complex of the radio telescope by special SNAP commands from both operator input and schedule files. We are also developing procedures of automatic measurements of SEFD, system noise temperature and other parameters, available both in VLBI and single-dish modes of operation. The system described has been installed on all IAA RAS radio telescopes at "Svetloe", "Zelenchukskaya" and "Badary" observatories. It has proved to be working quite reliably and to show the perfonmance expected.

  16. [Role of RAS in prehypertension].

    PubMed

    Inaba, Shinji; Iwai, Masaru; Horiuchi, Masatsugu

    2008-08-01

    Hypertension has long been recognized as a major risk factor of several cardiovascular diseases. It is well known that the renin-angiotensin system(RAS) is involved in the pathogenesis of both hypertension and hypertensive end-organ damage. Untreated hypertension is self-accelerating condition through RAS stimulation. Activation of RAS contributes to the transition from borderline hypertension to established hypertension. Recently, "the Seventh Report of Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7)" proposed a new classification of borderline blood pressure levels, as "prehypertension". The therapeutic focus has begun to shift from the therapy of established hypertension to the prevention of hypertension. This review addressed the relationship between hypertension, prehypertension and the role of RAS. PMID:18700549

  17. [Vernier Anode Design and Image Simulation].

    PubMed

    Zhao, Ai-rong; Ni, Qi-liang; Song, Ke-fei

    2015-12-01

    Based-MCP position-sensitive anode photon-counting imaging detector is good at detecting extremely faint light, which includes micro-channel plate (MCP), position-sensitive anode and readout, and the performances of these detectors are mainly decided by the position-sensitive anode. As a charge division anode, Vernier anode using cyclically varying electrode areas which replaces the linearly varying electrodes of wedge-strip anode can get better resolution and greater electrode dynamic range. Simulation and design of the Vernier anode based on Vernier's decode principle are given here. Firstly, we introduce the decode and design principle of Vernier anode with nine electrodes in vector way, and get the design parameters which are the pitch, amplitude and the coarse wavelength of electrode. Secondly, we analyze the effect of every design parameters to the imaging of the detector. We simulate the electron cloud, the Vernier anode and the detector imaging using Labview software and get the relationship between the pitch and the coarse wavelength of the anode. Simultaneously, we get the corresponding electron cloud for the designing parameters. Based on the result of the simulation and the practical machining demand, a nine electrodes Vernier anode was designed and fabricated which has a pitch of 891 µm, insulation width of 25 µm, amplitude of 50 µm, coarse pixel numbers of 5. PMID:26964205

  18. The Process Design Courses at Pennsylvania: Impact of Process Simulators.

    ERIC Educational Resources Information Center

    Seider, Warren D.

    1984-01-01

    Describes the use and impact of process design simulators in process design courses. Discusses topics covered, texts used, computer design simulations, and how they are integrated into the process survey course as well as in plant design projects. (JM)

  19. Designing Online Scaffolds for Interactive Computer Simulation

    ERIC Educational Resources Information Center

    Chen, Ching-Huei; Wu, I-Chia; Jen, Fen-Lan

    2013-01-01

    The purpose of this study was to examine the effectiveness of online scaffolds in computer simulation to facilitate students' science learning. We first introduced online scaffolds to assist and model students' science learning and to demonstrate how a system embedded with online scaffolds can be designed and implemented to help high…

  20. Thin-film designs by simulated annealing

    NASA Astrophysics Data System (ADS)

    Boudet, T.; Chaton, P.; Herault, L.; Gonon, G.; Jouanet, L.; Keller, P.

    1996-11-01

    With the increasing power of computers, new methods in synthesis of optical multilayer systems have appeared. Among these, the simulated-annealing algorithm has proved its efficiency in several fields of physics. We propose to show its performances in the field of optical multilayer systems through different filter designs.

  1. Dynamic Process Simulation for Analysis and Design.

    ERIC Educational Resources Information Center

    Nuttall, Herbert E., Jr.; Himmelblau, David M.

    A computer program for the simulation of complex continuous process in real-time in an interactive mode is described. The program is user oriented, flexible, and provides both numerical and graphic output. The program has been used in classroom teaching and computer aided design. Typical input and output are illustrated for a sample problem to…

  2. Design and Simulation of Hybridization Experiments

    Energy Science and Technology Software Center (ESTSC)

    1995-11-28

    DB EXP DESIGN is a suite of three UNIX shell-like programs, DWC which computes oligomer composition of DNA texts using directed acyclic word data structures; DWO, which simulates hybridization experiments; and DMI, which calculates the information contenet of individual probes, their mutual information content, and their joint information content through estimation of Markov trees.

  3. Symbolic computation in system simulation and design

    NASA Astrophysics Data System (ADS)

    Evans, Brian L.; Gu, Steve X.; Kalavade, Asa; Lee, Edward A.

    1995-06-01

    This paper examines some of the roles that symbolic computation plays in assisting system- level simulation and design. By symbolic computation, we mean programs like Mathematica that perform symbolic algebra and apply transformation rules based on algebraic identities. At a behavioral level, symbolic computation can compute parameters, generate new models, and optimize parameter settings. At the synthesis level, symbolic computation can work in tandem with synthesis tools to rewrite cascade and parallel combinations on components in sub- systems to meet design constraints. Symbolic computation represents one type of tool that may be invoked in the complex flow of the system design process. The paper discusses the qualities that a formal infrastructure for managing system design should have. The paper also describes an implementation of this infrastructure called DesignMaker, implemented in the Ptolemy environment, which manages the flow of tool invocations in an efficient manner using a graphical file dependency mechanism.

  4. Design and simulation of MEMS capacitive magnetometer

    NASA Astrophysics Data System (ADS)

    Jyoti, Aditi, Tripathi, C. C.; Gopal, Ram

    2016-04-01

    This paper presents the design and simulation of a MEMS Capacitive Magnetometer using FEM (Finite Element Method) tool COMSOL Multiphysics 4.3b and results from this simulation are closely matched with analytically calculated results. A comb drive structure is used for actuation purpose which operates at resonant frequency of device is 11.791 kHz to achieve maximum displacement. A magnetic field in z-axis can be detected by this comb drive structure. Quality factor of MEMS capacitive magnetometer obtained is 18 and it has good linear response in the magnetic field range of 100 µT.

  5. ALT-3 target design and simulations

    SciTech Connect

    Peterson, Jeffrey H

    2011-01-12

    ALT-3 is an experiment being designed in collaboration between Russian VNIIEF scientists and LANL that aims to conduct high velocity material experiments to measure shock velocities and pressures near 1 TPa. The DEMG (Disck Explosive Magnetic Generator) is used to drive> 60MA currents to accelerate an aluminum liner to speeds in excess of 20 km/s. 1-D and 2-D simulations of the aluminum target are presented with information on the free surface velocity profile, the state of the target, and the shock velocity in the target. 2-D simulations are presented showing the different targets available as well as a scenario with a perturbed liner impacter.

  6. Parachute system design, analysis, and simulation tool

    SciTech Connect

    Sundberg, W.D.; McBride, D.D.; Gwinn, K.W.; Waye, D.E.; Hailey, C.E.

    1992-01-01

    For over twenty years designers at Sandia National Laboratories have developed various parachute simulation codes to model deployment, inflation, loading, trajectories, aircraft downwash and line sail. In addition to these codes, material property data bases have been acquired. Recently we have initiated project to integrate these codes and data bases into a single software tool entitled SPARSYS (Sandia PARachute SYstem Simulation). We have constructed a graphical user interface as the driver and framework for SPARSYS. In this paper we present a status report on SPARSYS describing progress in developing and incorporating independent modules, in developing an integrated trajectory package, and in developing a materials data base including high-rate-of-strain data.

  7. Comparative proteomic analysis of compartmentalised Ras signalling

    PubMed Central

    Hernandez-Valladares, Maria; Prior, Ian A.

    2015-01-01

    Ras proteins are membrane bound signalling hubs that operate from both the cell surface and endomembrane compartments. However, the extent to which intracellular pools of Ras can contribute to cell signalling is debated. To address this, we have performed a global screen of compartmentalised Ras signalling. We find that whilst ER/Golgi- and endosomal-Ras only generate weak outputs, Ras localised to the mitochondria or Golgi significantly and distinctly influence both the abundance and phosphorylation of a wide range of proteins analysed. Our data reveal that ~80% of phosphosites exhibiting large (≥1.5-fold) changes compared to control can be modulated by organellar Ras signalling. The majority of compartmentalised Ras-specific responses are predicted to influence gene expression, RNA splicing and cell proliferation. Our analysis reinforces the concept that compartmentalisation influences Ras signalling and provides detailed insight into the widespread modulation of responses downstream of endomembranous Ras signalling. PMID:26620772

  8. Orbit Design and Simulation for Kufasat Nanosatellite

    NASA Astrophysics Data System (ADS)

    Mahdi, Mohammed Chessab

    2015-12-01

    Orbit design for KufaSat Nano-satellites is presented. Polar orbit is selected for the KufaSat mission. The orbit was designed with an Inclination which enables the satellite to see every part of the earth. KufaSat has a payload for imaging purposes which require a large amount of power, so the orbit is determined to be sun synchronous in order to provide the power through solar panels. The KufaSat mission is designed for the low earth orbit. The six initial Keplerian Elements of KufaSat are calculated. The orbit design of KufaSat according to the calculated Keplerian elements has been simulated and analyzed by using MATLAB first and then by using General Mission Analysis Tool.

  9. Cardiac remodelling and RAS inhibition.

    PubMed

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  10. Design and simulation of a neutron facility.

    PubMed

    Studenski, Matthew T; Kearfott, Kimberlee J

    2007-02-01

    State and other regulatory entities require that for any facility housing a particle accelerator the surrounding areas must be restricted to public access unless the dose equivalent rate is less than 0.02 mSv h at 5 cm from any accessible wall surrounding the facility under conditions of maximum radiation output. A Monte Carlo radiation transport simulation code, MCNP5, was used to design a proposed facility to shield two D-T neutron generators and one D-D neutron generator. A number of different designs were simulated, but due to cost and space issues a small concrete cave proved to be the best solution for the shielding problem. With this design, all of the neutron generators could be used and all of the rooms surrounding the neutron facility could be considered unrestricted to public access. To prevent unauthorized access into the restricted area of the neutron facility, light curtains, warning lights, door interlocks, and rope barriers will be built into the facility. PMID:17228186

  11. Simulated Data for High Temperature Composite Design

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Abumeri, Galib H.

    2006-01-01

    The paper describes an effective formal method that can be used to simulate design properties for composites that is inclusive of all the effects that influence those properties. This effective simulation method is integrated computer codes that include composite micromechanics, composite macromechanics, laminate theory, structural analysis, and multi-factor interaction model. Demonstration of the method includes sample examples for static, thermal, and fracture reliability for a unidirectional metal matrix composite as well as rupture strength and fatigue strength for a high temperature super alloy. Typical results obtained for a unidirectional composite show that the thermal properties are more sensitive to internal local damage, the longitudinal properties degrade slowly with temperature, the transverse and shear properties degrade rapidly with temperature as do rupture strength and fatigue strength for super alloys.

  12. Digital autopilots: Design considerations and simulator evaluations

    NASA Technical Reports Server (NTRS)

    Osder, S.; Neuman, F.; Foster, J.

    1971-01-01

    The development of a digital autopilot program for a transport aircraft and the evaluation of that system's performance on a transport aircraft simulator is discussed. The digital autopilot includes three axis attitude stabilization, automatic throttle control and flight path guidance functions with emphasis on the mode progression from descent into the terminal area through automatic landing. The study effort involved a sequence of tasks starting with the definition of detailed system block diagrams of control laws followed by a flow charting and programming phase and concluding with performance verification using the transport aircraft simulation. The autopilot control laws were programmed in FORTRAN 4 in order to isolate the design process from requirements peculiar to an individual computer.

  13. Therapeutic Strategies for Targeting Ras Proteins

    PubMed Central

    Gysin, Stephan; Salt, Megan; Young, Amy; McCormick, Frank

    2011-01-01

    Ras genes are frequently activated in cancer. Attempts to develop drugs that target mutant Ras proteins have, so far, been unsuccessful. Tumors bearing these mutations, therefore, remain among the most difficult to treat. Most efforts to block activated Ras have focused on pathways downstream. Drugs that inhibit Raf kinase have shown clinical benefit in the treatment of malignant melanoma. However, these drugs have failed to show clinical benefit in Ras mutant tumors. It remains unclear to what extent Ras depends on Raf kinase for transforming activity, even though Raf proteins bind directly to Ras and are certainly major effectors of Ras action in normal cells and in development. Furthermore, Raf kinase inhibitors can lead to paradoxical activation of the MAPK pathway. MEK inhibitors block the Ras-MAPK pathway, but often activate the PI3’-kinase, and have shown little clinical benefit as single agents. This activation is mediated by EGF-R and other receptor tyrosine kinases through relief of a negative feedback loop from ERK. Drug combinations that target multiple points within the Ras signaling network are likely to be necessary to achieve substantial clinical benefit. Other effectors may also contribute to Ras signaling and provide a source of targets. In addition, unbiased screens for genes necessary for Ras transformation have revealed new potential targets and have added to our understanding of Ras cancer biology. PMID:21779505

  14. VOCs monitoring system simulation and design

    NASA Astrophysics Data System (ADS)

    Caldararu, Florin; Vasile, Alexandru; Vatra, Cosmin

    2010-11-01

    The designed and simulated system will be used in the tanning industry, for Volatile Organic Compound (VOC) measurements. In this industry, about 90% of the solvent contained in the emulsions evaporates during its application, giving rise to VOC, which are at the same time hazardous atmospheric pollutants and one of the sources of ground level photochemical ozone formation. It results that a monitoring system is necessary in a leather finishing process, in order to detect hazardous VOC concentration and conducting process in order of VOC concentration diminishing. The paper presents the design of a VOC monitoring system, which includes sensors for VOCs and temperature, the conditioning circuitry for these sensors, the suction system of the gas in the hood, the data acquisition and the computing system and graphic interface. The used sensor in the detection system is a semiconductor sensor, produced by Figaro Engineering Inc., characterized by a short response time, high sensitivity at almost all VOC substances. The design of the conditioning circuitry and data acquisition is done in order to compensate the sensor response variation with temperature and to maintain the low response time of the sensor. The temperature compensation is obtained by using a thermistor circuitry, and the compensation is done within the software design. A Mitsubishi PLC is used to receive the output signals of the circuits including the sensor and of the thermistor, respectively. The acquisition and computing system is done using Mitsubishi ALPHA 2 controller and a graphical terminal, GOT 1000.

  15. Simulation-based disassembly systems design

    NASA Astrophysics Data System (ADS)

    Ohlendorf, Martin; Herrmann, Christoph; Hesselbach, Juergen

    2004-02-01

    Recycling of Waste of Electrical and Electronic Equipment (WEEE) is a matter of actual concern, driven by economic, ecological and legislative reasons. Here, disassembly as the first step of the treatment process plays a key role. To achieve sustainable progress in WEEE disassembly, the key is not to limit analysis and planning to merely disassembly processes in a narrow sense, but to consider entire disassembly plants including additional aspects such as internal logistics, storage, sorting etc. as well. In this regard, the paper presents ways of designing, dimensioning, structuring and modeling different disassembly systems. Goal is to achieve efficient and economic disassembly systems that allow recycling processes complying with legal requirements. Moreover, advantages of applying simulation software tools that are widespread and successfully utilized in conventional industry sectors are addressed. They support systematic disassembly planning by means of simulation experiments including consecutive efficiency evaluation. Consequently, anticipatory recycling planning considering various scenarios is enabled and decisions about which types of disassembly systems evidence appropriateness for specific circumstances such as product spectrum, throughput, disassembly depth etc. is supported. Furthermore, integration of simulation based disassembly planning in a holistic concept with configuration of interfaces and data utilization including cost aspects is described.

  16. Ras in Cancer and Developmental Diseases

    PubMed Central

    Fernández-Medarde, Alberto; Santos, Eugenio

    2011-01-01

    Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies. PMID:21779504

  17. Design and simulation of e-calendar system circuits

    NASA Astrophysics Data System (ADS)

    Liu, Li-jun

    2015-02-01

    The digital calendar circuits controlled by 80C52 have been designed based on Proteus simulation software. The whole design process is made of three parts: hardware circuits, software programming and software simulation. Finally, it shows that the circuit design of hardware and software is correct through Proteus software simulation. The method of circuit design is systematic and practical, which will provide certain design ideas and reference value for display circuit in the future.

  18. Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

    PubMed Central

    Pathan, Akbar Ali Khan; Panthi, Bhavana; Khan, Zahid; Koppula, Purushotham Reddy; Alanazi, Mohammed Saud; Sachchidanand; Parine, Narasimha Reddy; Chourasia, Mukesh

    2016-01-01

    Objective Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results Interestingly, the designed compounds exhibit a binding preference for the “off” state over “on” state conformation of K-Ras protein. Moreover, the designed compounds’ interactions are similar to guanosine diphosphate and, thus, could presumably act as a potential lead for K-Ras. The predicted drug-likeness properties of these compounds suggest that these compounds follow the Lipinski’s rule of five and have tolerable absorption, distribution, metabolism, excretion and toxicity values. Conclusion Thus, through the current study, we propose targeting only “off” state conformations as a promising strategy for the design of reversible inhibitors to pharmacologically inhibit distinct conformations of K-Ras protein. PMID:27217775

  19. Muon RLA - design status and simulations

    NASA Astrophysics Data System (ADS)

    Beard, K. B.; Bogacz, S. A.; Morozov, V. S.; Roblin, Y. R.

    2013-02-01

    The Neutrino Factory baseline design involves a complex chain of accelerators beginning with a linac. This first pre-linac follows the capture and bunching section and accelerates the muons from about 244 to 900 MeV and must accept a high emittance beam about 30 cm wide with a 10% energy spread. It uses counterwound, shielded superconducting solenoids and 201 MHz superconducting cavities, and currently consists of 24 3 m and 24 5 m long cryomodules. The next stage is a 1st dogbone-shaped RLA that takes the total energy from 900 MeV to 3.6 GeV in 4.5 passes, followed by a 2nd RLA that takes the energy from 3.6 to 12.6 GeV in 4.5 passes. Simulations are in progress to optimize the optics and determine the radiation loads from beam loss and muon decay.

  20. Innovations in infrared scene simulator design

    NASA Astrophysics Data System (ADS)

    Lane, Richard; Heath, Jeffery L.

    1998-07-01

    The MIRAGE (Multispectral Infrared Animation Generation Equipment) Dynamic Infrared Scene Projector, is a joint project developed by Santa Barbara Infrared, Inc. and Indigo Systems Corporation. MIRAGE is a complete infrared scene projector, accepting 3-D rendered analog or digital scene data at its input, and providing all other electronics, collimated optics, calibration and thermal support subsystems needed to simulated a unit under test with high-fidelity, dynamic infrared scenes. At the heart of MIRAGE is a 512 X 512 emitter array, with key innovations that solve several problems of existing designs. The read-in integrated circuit (RIIC) features 'snapshot' updating of the entire 512 X 512 resistive array, thus solving synchronization and latency problems inherent in 'rolling- update' type designs, where data is always changing somewhere on the emitter array at any given time. This custom mixed- signal RIIC also accepts digital scene information at its input, and uses on-board D/A converters and individual unit- cell buffer amplifiers to create analog scene levels, eliminating the complexity, noise, and limitations of speed and dynamic range associated with external generation of analog scene levels. The proprietary process used to create the advanced technology micro-membrane emitter elements allows a wide choice of resistor and structure materials while preserving the dissipation and providing a thermal time constant of the order of 5 ms. These innovations, along with a compact electronics subsystem based on a standard desktop PC, greatly reduce the complexity of the required external support electronics, resulting in a smaller, higher performance dynamic scene simulator system.

  1. How to Target Activated Ras Proteins: Direct Inhibition vs. Induced Mislocalization.

    PubMed

    Brock, Ethan J; Ji, Kyungmin; Reiners, John J; Mattingly, Raymond R

    2016-01-01

    Oncogenic Ras proteins are a driving force in a significant set of human cancers and wildtype, unmutated Ras proteins likely contribute to the malignant phenotype of many more. The overall challenge of targeting activated Ras proteins has great promise to treat cancer, but this goal has yet to be achieved. Significant efforts and resources have been committed to inhibiting Ras, but these energies have so far made little impact in the clinic. Direct attempts to target activated Ras proteins have faced many obstacles, including the fundamental nature of the gain-of-function oncogenic activity being produced by a loss-of-function at the biochemical level. Nevertheless, there has been very promising recent pre-clinical progress. The major strategy that has so far reached the clinic aimed to inhibit activated Ras indirectly through blocking its post-translational modification and inducing its mislocalization. While these efforts to indirectly target Ras through inhibition of farnesyl transferase (FTase) were rationally designed, this strategy suffered from insufficient attention to the distinctions between the isoforms of Ras. This led to subsequent failures in large-scale clinical trials targeting K-Ras driven lung, colon, and pancreatic cancers. Despite these setbacks, efforts to indirectly target activated Ras through inducing its mislocalization have persisted. It is plausible that FTase inhibitors may still have some utility in the clinic, perhaps in combination with statins or other agents. Alternative approaches for inducing mislocalization of Ras through disruption of its palmitoylation cycle or interaction with chaperone proteins are in early stages of development. PMID:26423696

  2. Modeling the Transcriptional Consequences of Epidermal Growth Factor Receptor Ablation in Ras-Initiated Squamous Cancer

    PubMed Central

    Wright, Lisa Nolan; Ryscavage, Andrew; Merlino, Glenn; Yuspa, Stuart H.

    2011-01-01

    Purpose EGFR targeted therapy is in clinical use to treat squamous cell carcinoma of the head and neck and other cancers of lining epithelium. Ras mutations in these tumors are a negative prognostic factor for response and skin inflammation is an adverse reaction to therapy. We investigated transcriptional and biochemical changes that could account for the confounding effects of RAS activation and inflammation in a squamous tissue. Experimental Design We performed gene expression profiling on oncogenic Ras transformed and wildtype mouse and human keratinocytes with EGFR ablated chronically by genetic deletion or acutely by drug treatment and followed leads provided by pathway analysis with biochemical studies. Results We identified a 25 gene signature specific to the Ras-EGFR ablation interaction and a distinct 19 gene EGFR ablation signature on normal keratinocytes. EGFR ablation in the context of wildtype Ras reduces ontologies favoring cell cycle control and transcription while oncogenic Ras enriches ontologies for ion channels and membrane transporters, particularly focused on calcium homeostasis. Ontologies between chronic EGFR ablation and acute pharmacological ablation were unique, both with and without Ras activation. p38α is activated in response to abrogation of EGFR signaling under conditions of Ras activation in both mouse and human keratinocytes and in RAS transformed tumor orthografts of EGFR ablated mouse keratinocytes. EGFR ablation in the absence of oncogenic Ras revealed Erk and IL-1β related pathways. Conclusion These findings reveal unrecognized interactions between Ras and EGFR signaling in squamous tumor cells that could influence the therapeutic response to EGFR ablation therapy. PMID:22068661

  3. Constructivist Design of Graphic Computer Simulations.

    ERIC Educational Resources Information Center

    Black, John B.; And Others

    Two graphic computer simulations have been prepared for teaching high school and middle school students about how business organizations and financial systems work: "Parkside," which simulates managing a hotel; and "Guestwear," which simulates managing a clothing manufacturer. Both simulations are based on six principles of constructivist design…

  4. Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

    PubMed Central

    Menachem, A; Bodner, O; Pastor, J; Raz, A; Kloog, Y

    2015-01-01

    Anaplastic Thyroid carcinoma is an extremely aggressive solid tumor that resists most treatments and is almost always fatal. Galectin-3 (Gal-3) is an important marker for thyroid carcinomas and a scaffold of the K-Ras protein. S-trans, transfarnesylthiosalicylic acid (FTS; Salirasib) is a Ras inhibitor that inhibits the active forms of Ras proteins. Modified citrus pectin (MCP) is a water-soluble citrus-fruit-derived polysaccharide fiber that specifically inhibits Gal-3. The aim of this study was to develop a novel drug combination designed to treat aggressive anaplastic thyroid carcinoma. Combined treatment with FTS and MCP inhibited anaplastic thyroid cells proliferation in vitro by inducing cell cycle arrest and increasing apoptosis rate. Immunoblot analysis revealed a significant decrease in Pan-Ras, K-Ras, Ras-GTP, p-ERK, p53, and Gal-3 expression levels and significant increase in p21 expression levels. In nude mice, treatment with FTS and MCP inhibited tumor growth. Levels of Gal-3, K-Ras-GTP, and p-ERK were significantly decreased. To conclude, our results suggest K-Ras and Gal-3 as potential targets in anaplastic thyroid tumors and herald a novel treatment for highly aggressive anaplastic thyroid carcinoma. PMID:27551476

  5. A computer simulator for development of engineering system design methodologies

    NASA Technical Reports Server (NTRS)

    Padula, S. L.; Sobieszczanski-Sobieski, J.

    1987-01-01

    A computer program designed to simulate and improve engineering system design methodology is described. The simulator mimics the qualitative behavior and data couplings occurring among the subsystems of a complex engineering system. It eliminates the engineering analyses in the subsystems by replacing them with judiciously chosen analytical functions. With the cost of analysis eliminated, the simulator is used for experimentation with a large variety of candidate algorithms for multilevel design optimization to choose the best ones for the actual application. Thus, the simulator serves as a development tool for multilevel design optimization strategy. The simulator concept, implementation, and status are described and illustrated with examples.

  6. Targeting oncogenic Ras signaling in hematologic malignancies

    PubMed Central

    Ward, Ashley F.; Braun, Benjamin S.

    2012-01-01

    Ras proteins are critical nodes in cellular signaling that integrate inputs from activated cell surface receptors and other stimuli to modulate cell fate through a complex network of effector pathways. Oncogenic RAS mutations are found in ∼ 25% of human cancers and are highly prevalent in hematopoietic malignancies. Because of their structural and biochemical properties, oncogenic Ras proteins are exceedingly difficult targets for rational drug discovery, and no mechanism-based therapies exist for cancers with RAS mutations. This article reviews the properties of normal and oncogenic Ras proteins, the prevalence and likely pathogenic role of NRAS, KRAS, and NF1 mutations in hematopoietic malignancies, relevant animal models of these cancers, and implications for drug discovery. Because hematologic malignancies are experimentally tractable, they are especially valuable platforms for addressing the fundamental question of how to reverse the adverse biochemical output of oncogenic Ras in cancer. PMID:22898602

  7. Optical design of MAORY turbulence simulator

    NASA Astrophysics Data System (ADS)

    Lombini, Matteo; Diolaiti, Emiliano; Arcidiacono, Carmelo; Bregoli, Giovanni; Cosentino, Giuseppe; De Rosa, Adriano; Foppiani, Italo; Schreiber, Laura

    2013-12-01

    MAORY, the foreseen multi conjugate adaptive optics module for the Extremely Large Telescope, has the goal to relay the telescope focal plane achieving a high and uniform correction of the atmosphere induced wavefront aberrations, over a 2 arcmin field of view in a large fraction of the sky. The aberrated wavefronts will be measured by 6 Sodium laser guide stars, arranged symmetrically over a 2 arcmin circular field of view, and by 3 natural guide stars in a searching field of view up to 2.6 arcmin and will be corrected by means of the telescope embedded adaptive mirror M4 and two post focal deformable mirrors. At the end of the integration phase performance tests of MAORY adaptive correction capability must be carried out. We present in this paper the optical design of a turbulence generator that will feed the MAORY entrance focal plane with sources representing laser and natural guide stars with realistic time varying aberrated wavefronts. The focal plane diameter (~500 mm) and the distance between the natural and the laser guide star focal plane positions (4-6 m) discourage a monolithic design of the turbulence generator. Our approach consists in separating the optical paths of the different sources in order to use smaller and thus more feasible components. The time varying atmospheric turbulence at several altitudes over the telescope is planned to be carried out placing before the pupil stop few phase screens on moving stages. Set of mirrors focus both the natural and laser stars at the expected positions of the real sources, preserving the telescope optical parameters as the exit pupil position, focal ratio, field curvature. Three laser guide stars and seven natural guide stars, one on axis and 6 at 1 arcmin off-axis, can be simulated with diffraction limit size.

  8. RAS and Hedgehog--partners in crime.

    PubMed

    Lauth, Matthias

    2011-01-01

    Both RAS and Hedgehog (HH) pathway activation can be found in approximately one third of all cancers. In many cases, this activation occurs in the same tumor types, suggesting a positive impact of a simultaneous activation of RAS and HH on tumor development. This review aims to summarize the current knowledge about the molecular and functional crosstalk of RAS and HH signaling in the development of hyperproliferative disease. PMID:21622175

  9. RAS oncogenes: weaving a tumorigenic web

    PubMed Central

    Pylayeva-Gupta, Yuliya; Grabocka, Elda; Bar-Sagi, Dafna

    2013-01-01

    RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. Oncogenic activation of these proteins owing to missense mutations is frequently detected in several types of cancer. A wealth of biochemical and genetic studies indicates that RAS proteins control a complex molecular circuitry that consists of a wide array of interconnecting pathways. In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis. PMID:21993244

  10. Simulation Tools Model Icing for Aircraft Design

    NASA Technical Reports Server (NTRS)

    2012-01-01

    Here s a simple science experiment to try: Place an unopened bottle of distilled water in your freezer. After 2-3 hours, if the water is pure enough, you will notice that it has not frozen. Carefully pour the water into a bowl with a piece of ice in it. When it strikes the ice, the water will instantly freeze. One of the most basic and commonly known scientific facts is that water freezes at around 32 F. But this is not always the case. Water lacking any impurities for ice crystals to form around can be supercooled to even lower temperatures without freezing. High in the atmosphere, water droplets can achieve this delicate, supercooled state. When a plane flies through clouds containing these droplets, the water can strike the airframe and, like the supercooled water hitting the ice in the experiment above, freeze instantly. The ice buildup alters the aerodynamics of the plane - reducing lift and increasing drag - affecting its performance and presenting a safety issue if the plane can no longer fly effectively. In certain circumstances, ice can form inside aircraft engines, another potential hazard. NASA has long studied ways of detecting and countering atmospheric icing conditions as part of the Agency s efforts to enhance aviation safety. To do this, the Icing Branch at Glenn Research Center utilizes a number of world-class tools, including the Center s Icing Research Tunnel and the NASA 607 icing research aircraft, a "flying laboratory" for studying icing conditions. The branch has also developed a suite of software programs to help aircraft and icing protection system designers understand the behavior of ice accumulation on various surfaces and in various conditions. One of these innovations is the LEWICE ice accretion simulation software. Initially developed in the 1980s (when Glenn was known as Lewis Research Center), LEWICE has become one of the most widely used tools in icing research and aircraft design and certification. LEWICE has been transformed over

  11. Suppression of ras-transformants (review).

    PubMed

    Kuzumaki, N

    1991-01-01

    Transforming ras genes are the oncogenes most frequently identified in human cancers. This justifies the intense interest in finding ways to suppress oncogenicity in these gene family-mediated transformants. The methods of suppression can be classified as 1) genetical, 2) biological and 3) pharmacological. Most of the reagents used for the suppression inhibit rodent transformants induced by transfected viral or activated cellular ras oncogenes, but some of the reagents are also effective when applied to natural human transformants that contain activated ras oncogenes. The growth and tumorigenicity of the ras-transformants are suppressed by the inhibition of the integration, transcription, translation or post-translational modification of the ras genes and p21 ras proteins, as well as the inhibition of the expression of genes which collaborate in the ras-transformation or the enhancement of some tumor suppressor genes. These observations offer novel approaches to the investigation of malignant transformation by ras-oncogenes, and have potential application in treatment of ras-oncogene-induced tumors. PMID:2018365

  12. Ras trafficking, localization and compartmentalized signalling

    PubMed Central

    Prior, Ian A.; Hancock, John F.

    2012-01-01

    Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes. PMID:21924373

  13. Telecom Link--A Competitive Simulated Design Exercise.

    ERIC Educational Resources Information Center

    Freeman, J.; Allen, J.

    1982-01-01

    Telecom link is a structured design exercise concerned with building a telecommunications link between London and Amsterdam. Designed for A-level physics, the simulation requires a minimum of 10 hours. Aims of the exercise, design specifications and technical aspects, and summaries of four possible technologies used in the simulation are…

  14. Designing with Ada for satellite simulation: A case study

    NASA Technical Reports Server (NTRS)

    Agresti, W. W.; Church, V. E.; Card, D. N.; Lo, P. L.

    1986-01-01

    A FORTRAN oriented and an Ada oriented design for the same system are compared to learn whether an essentially different design was produced using Ada. The designs were produced by an experiment that involves the parallel development of software for a spacecraft dynamics simulator. Design differences are identified in the use of abstractions, system structure, and simulator operations. Although the designs were vastly different, this result may be influenced by some special characteristics discussed.

  15. Designing with Ada for satellite simulation: A case study

    NASA Technical Reports Server (NTRS)

    Agresti, William W.; Church, Victor E.; Card, David N.; Lo, P. L.

    1986-01-01

    A FORTRAN-operated and an Ada-oriented design for the same system are compared to learn whether an essentially different design was produced using Ada. The designs were produced by an experiment that involves the parallel development of software for a spacecraft dynamics simulator. Design differences are identified in the use of abstractions, system structure, and simulator operations. Although the designs were significantly different, this result may be influenced by some special characteristics discussed.

  16. Expression, Purification, and Characterization of Ras Protein (BmRas1) from Bombyx mori

    PubMed Central

    Quan, Yanping; Liu, Guangqiang; Yu, Wei; Nie, Zuoming; Chen, Jian; Lv, Zhengbing; Zhang, Yaozhou

    2012-01-01

    The Ras subfamily is the member of small G proteins superfamily involved in cellular signal transduction. Activation of Ras signaling causes cell growth, differentiation, and survival. Bombyx mori Ras-like protein (BmRas1) may belong to the Ras subfamily. It contained an H-N-K-Ras-like domain. The BmRas1 mRNA consisted of 1459 bp. The open reading frame contained 579 bp, encoding 192 amino acids. The protein had such secondary structures as α-helices, extended strand, and random coil. BmRas1 was expressed successfully in E. coli BL21. The recombinant protein was purified with metal-chelating affinity chromatography. The GTPase activity of purified protein was determined by FeSO4-(NH4)2MoO4 assay. The results showed that purified recombinant protein had intrinsic activity of GTPase. High titer polyclonal antibodies were generated by New Zealand rabbit immunized with purified protein. The gene expression features of BmRas1 at different stages and in different organs of the fifth instar larvae were analyzed by Western blot. The results showed that BmRas1 was expressed highly in three development stages including egg, pupae, and adult, but low expression in larva. BmRas1 was expressed in these tissues including head, malpighian tubule, genital gland, and silk gland. The purified recombinant protein would be utilized to further function studies of BmRas1. PMID:22536118

  17. Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

    PubMed Central

    Buhrman, Greg; O’Connor, Casey; Zerbe, Brandon; Kearney, Bradley M.; Napoleon, Raeanne; Kovrigina, Elizaveta A.; Vajda, Sandor; Kozakov, Dima; Kovrigin, Evgenii L.; Mattos, Carla

    2011-01-01

    We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the “off” and “on” allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target. PMID:21945529

  18. Design and simulation of lithium rechargeable batteries

    SciTech Connect

    Doyle, C.M.

    1995-08-01

    Lithium -based rechargeable batteries that utilize insertion electrodes are being considered for electric-vehicle applications because of their high energy density and inherent reversibility. General mathematical models are developed that apply to a wide range of lithium-based systems, including the recently commercialized lithium-ion cell. The modeling approach is macroscopic, using porous electrode theory to treat the composite insertion electrodes and concentrated solution theory to describe the transport processes in the solution phase. The insertion process itself is treated with a charge-transfer process at the surface obeying Butler-Volmer kinetics, followed by diffusion of the lithium ion into the host structure. These models are used to explore the phenomena that occur inside of lithium cells under conditions of discharge, charge, and during periods of relaxation. Also, in order to understand the phenomena that limit the high-rate discharge of these systems, we focus on the modeling of a particular system with well-characterized material properties and system parameters. The system chosen is a lithium-ion cell produced by Bellcore in Red Bank, NJ, consisting of a lithium-carbon negative electrode, a plasticized polymer electrolyte, and a lithium-manganese-oxide spinel positive electrode. This battery is being marketed for consumer electronic applications. The system is characterized experimentally in terms of its transport and thermodynamic properties, followed by detailed comparisons of simulation results with experimental discharge curves. Next, the optimization of this system for particular applications is explored based on Ragone plots of the specific energy versus average specific power provided by various designs.

  19. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

    PubMed Central

    Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

    2016-01-01

    Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP–GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID:26902995

  20. Ras-Mediated Deregulation of the Circadian Clock in Cancer

    PubMed Central

    Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

    2014-01-01

    Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock. PMID:24875049

  1. Ras-mediated deregulation of the circadian clock in cancer.

    PubMed

    Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

    2014-01-01

    Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock. PMID:24875049

  2. AVCS Simulator Test Plan and Design Guide

    NASA Technical Reports Server (NTRS)

    Shelden, Stephen

    2001-01-01

    Internal document for communication of AVCS direction and documentation of simulator functionality. Discusses methods for AVCS simulation evaluation of pilot functions, implementation strategy of varying functional representation of pilot tasks (by instantiations of a base AVCS to reasonably approximate the interface of various vehicles -- e.g. Altair, GlobalHawk, etc.).

  3. Phobos: Simulation-Driven Design for Exploration

    NASA Technical Reports Server (NTRS)

    Crues, Edwin

    2015-01-01

    Dr. Edwin "Zack" Crues presented an overview of the current use of modeling and simulation technologies by the NASA Exploration Systems Simulations (NExSyS) team in investigating the spacecraft and missions for the human exploration of Mars' moon Phobos.

  4. Differential activation of yeast adenylyl cyclase by Ras1 and Ras2 depends on the conserved N terminus.

    PubMed

    Hurwitz, N; Segal, M; Marbach, I; Levitzki, A

    1995-11-21

    Although both Ras1 and Ras2 activate adenylyl cyclase in yeast, a number of differences can be observed regarding their function in the cAMP pathway. To explore the relative contribution of conserved and variable domains in determining these differences, chimeric RAS1-RAS2 or RAS2-RAS1 genes were constructed by swapping the sequences encoding the variable C-terminal domains. These constructs were expressed in a cdc25ts ras1 ras2 strain. Biochemical data show that the difference in efficacy of adenylyl cyclase activation between the two Ras proteins resides in the highly conserved N-terminal domain. This finding is supported by the observation that Ras2 delta, in which the C-terminal domain of Ras2 has been deleted, is a more potent activator of the yeast adenylyl cyclase than Ras1 delta, in which the C-terminal domain of Ras1 has been deleted. These observations suggest that amino acid residues other than the highly conserved residues of the effector domain within the N terminus may determine the efficiency of functional interaction with adenylyl cyclase. Similar levels of intracellular cAMP were found in Ras1, Ras1-Ras2, Ras1 delta, Ras2, and Ras2-Ras1 strains throughout the growth curve. This was found to result from the higher expression of Ras1 and Ras1-Ras2, which compensate for their lower efficacy in activating adenylyl cyclase. These results suggest that the difference between the Ras1 and the Ras2 phenotype is not due to their different efficacy in activating the cAMP pathway and that the divergent C-terminal domains are responsible for these differences, through interaction with other regulatory elements. PMID:7479926

  5. Optimizing depuration of salmon in RAS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fish cultured within water recirculating aquaculture systems (RAS) can acquire "earthy" or "musty" off-flavors due to bioaccumulation of the compounds geosmin and 2-methylisoborneol (MIB), respectively, which are produced by certain bacterial species present in RAS biosolids and microbial biofilms. ...

  6. Integrated simulation environment for lighting design

    SciTech Connect

    Pal, Vineeta; Papamichael, Konstantinos

    2001-05-24

    Lighting design involves the consideration of multiple performance criteria, from the earliest stages of conceptual design, through various stages of controls and operation in a project's life cycle. These criteria include: (1) the quantitative analysis of illuminance and luminance distribution due to daylighting and electric lighting; (2) qualitative analysis of the lighting design with photometrically accurate renderings of the designed environment; (3) analysis of energy implications of daylighting and electric lighting design and operation;, and (4) analysis of control strategies and sensor placement for maximizing energy savings from lighting control while providing visual comfort. In this paper we describe the development of an integrated decision-making environment that brings together several different tools, and provides the data management and process control required for a multi-criterion support of the design and operation of daylighting and electric lighting systems. The result is a powerful design and decision-making environment to meet the diverse and evolving needs of lighting designers and operators.

  7. Established and emerging fluorescence-based assays for G-protein function: Ras-superfamily GTPases.

    PubMed

    Rojas, Rafael J; Kimple, Randall J; Rossman, Kent L; Siderovski, David P; Sondek, John

    2003-06-01

    Ras and Rho GTPases are signaling proteins that regulate a variety of physiological events and are intimately linked to the progression of cancer. Recently, a variety of fluorescence-based assays have been refined to monitor activation of these GTPases. This review summarizes current fluorescence-based techniques for studying Ras superfamily GTPases with an emphasis on practical examples and high-throughput applications. These techniques are not only useful for biochemical characterization of Ras superfamily members, but will also facilitate the discovery of small molecule therapeutics designed to inhibit signal transduction mediated by GTPases. PMID:12769685

  8. Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1

    PubMed Central

    Iwig, Jeffrey S; Vercoulen, Yvonne; Das, Rahul; Barros, Tiago; Limnander, Andre; Che, Yan; Pelton, Jeffrey G; Wemmer, David E; Roose, Jeroen P; Kuriyan, John

    2013-01-01

    RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI: http://dx.doi.org/10.7554/eLife.00813.001 PMID:23908768

  9. A New View of Ras Isoforms in Cancers.

    PubMed

    Nussinov, Ruth; Tsai, Chung-Jung; Chakrabarti, Mayukh; Jang, Hyunbum

    2016-01-01

    Does small GTPase K-Ras4A have a single state or two states, one resembling K-Ras4B and the other N-Ras? A recent study of K-Ras4A made the remarkable observation that even in the absence of the palmitoyl, K-Ras4A can be active at the plasma membrane. Importantly, this suggests that K-Ras4A may exist in two distinct signaling states. In state 1, K-Ras4A is only farnesylated, like K-Ras4B; in state 2, farnesylated and palmitoylated, like N-Ras. The K-Ras4A hypervariable region sequence is positively charged, in between K-Ras4B and N-Ras. Taken together, this raises the possibility that the farnesylated but nonpalmitoylated state 1, like K-Ras4B, binds calmodulin and is associated with colorectal and other adenocarcinomas like lung cancer and pancreatic ductal adenocarcinoma. On the other hand, state 2 may be associated with melanoma and other cancers where N-Ras is a major contributor, such as acute myeloid leukemia. Importantly, H-Ras has two, singly and doubly, palmitoylated states that may also serve distinct functional roles. The multiple signaling states of palmitoylated Ras isoforms question the completeness of small GTPase Ras isoform statistics in different cancer types and call for reevaluation of concepts and protocols. They may also call for reconsideration of oncogenic Ras therapeutics. PMID:26659836

  10. Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

    PubMed Central

    Cox, Adrienne D.; Der, Channing J.; Philips, Mark R.

    2015-01-01

    RAS proteins require membrane association for their biological activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTIs) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anti-cancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated post-translational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. PMID:25878363

  11. Some Current Problems in Simulator Design, Testing and Use.

    ERIC Educational Resources Information Center

    Caro, Paul W.

    Concerned with the general problem of the effectiveness of simulator training, this report reflects information developed during the conduct of aircraft simulator training research projects sponsored by the Air Force, Army, Navy, and Coast Guard. Problems are identified related to simulator design, testing, and use, all of which impact upon…

  12. Mechanical design of NASA Ames Research Center vertical motion simulator

    NASA Technical Reports Server (NTRS)

    Engelbert, D. F.; Bakke, A. P.; Chargin, M. K.; Vallotton, W. C.

    1976-01-01

    NASA has designed and is constructing a new flight simulator with large vertical travel. Several aspects of the mechanical design of this Vertical Motion Simulator (VMS) are discussed, including the multiple rack and pinion vertical drive, a pneumatic equilibration system, and the friction-damped rigid link catenaries used as cable supports.

  13. Automated simulation as part of a design workstation

    NASA Technical Reports Server (NTRS)

    Cantwell, Elizabeth; Shenk, T.; Robinson, P.; Upadhye, R.

    1990-01-01

    A development project for a design workstation for advanced life-support systems (called the DAWN Project, for Design Assistant Workstation), incorporating qualitative simulation, required the implementation of a useful qualitative simulation capability and the integration of qualitative and quantitative simulation such that simulation capabilities are maximized without duplication. The reason is that to produce design solutions to a system goal, the behavior of the system in both a steady and perturbed state must be represented. The Qualitative Simulation Tool (QST), on an expert-system-like model building and simulation interface toll called ScratchPad (SP), and on the integration of QST and SP with more conventional, commercially available simulation packages now being applied in the evaluation of life-support system processes and components are discussed.

  14. M-Ras induces Ral and JNK activation to regulate MEK/ERK-independent gene expression in MCF-7 breast cancer cells

    PubMed Central

    Castro, Ariel F.; Campos, Tania; Babcock, Justin T.; Armijo, Marisol E.; Martinez-Conde, Alfonso; Pincheira, Roxana; Quilliam, Lawrence A.

    2011-01-01

    Constitutive activation of M-Ras has previously been reported to cause morphologic and growth transformation of murine cells, suggesting that M-Ras plays a role in tumorigenesis. Cell transformation by M-Ras correlated with weak activation of the Raf/MEK/ERK pathway, although contributions from other downstream effectors were suggested. Recent studies indicate that signaling events distinct from the Raf/MEK/ERK cascade are critical for human tumorigenesis. However, it is unknown what signaling events M-Ras triggers in human cells. Using constitutively active M-Ras (Q71L) containing additional mutations within its effector binding loop, we found that M-Ras induces MEK/ERK-dependent and -independent Elk1 activation as well as PI3K/Akt and JNK/cJun activation in human MCF-7 breast cancer cells. Among several human cell lines examined, M-Ras-induced MEK/ERK-independent Elk1 activation was only detected in MCF-7 cells, and correlated with Rlf /M-Ras interaction and Ral /JNK activation. Supporting a role for M-Ras signaling in breast cancer, EGF activated M-Ras and promoted its interaction with endogenous Rlf. In addition, constitutive activation of M-Ras induced estrogen-independent growth of MCF-7 cells that was dependent on PI3K/Akt, MEK/ERK and JNK activation. Thus, our studies demonstrate that M-Ras signaling activity differs between human cells, highlighting the importance of defining Ras protein signaling within each cell type, especially when designing treatments for Ras-induced cancer. These findings also demonstrate that M-Ras activity may be important for progression of EGFR-dependent tumors. PMID:22121046

  15. Simulation Packages Expand Aircraft Design Options

    NASA Technical Reports Server (NTRS)

    2013-01-01

    In 2001, NASA released a new approach to computational fluid dynamics that allows users to perform automated analysis on complex vehicle designs. In 2010, Palo Alto, California-based Desktop Aeronautics acquired a license from Ames Research Center to sell the technology. Today, the product assists organizations in the design of subsonic aircraft, space planes, spacecraft, and high speed commercial jets.

  16. Design and Simulation of MEMS Enabled Systems

    NASA Astrophysics Data System (ADS)

    da Silva, Mark

    2001-03-01

    Over the past two decades considerable progress in microsystems (MEMS) fabrication technologies has been made resulting in a variety of commercially successful devices. Most of these devices have required application specific fabrication steps, which must be developed, and the lack of proper design tools often resulted in repeated prototyping that was expensive and time consuming. Further development of MEMS enabled commercial products and reduction of the time to market requires implementation of a concurrent design methodology through better design tools and standardization of the fabrication processes. The cross-disciplinary nature of MEMS-Enabled Systems necessitates designers with different backgrounds to work together in understanding the effects of one sub-system on another and this requires a top-down approach to integrated system design. Design tools that can facilitate this communication and reduce the need for excessive prototype fabrication and test iterations and significantly reduce cost and time-to-market are vitally important. The main focus of this article is to describe the top-down design methodology and and ongoing research on tools that facilitate concurrent design of MEMS enabled systems.

  17. Optimum spaceborne computer system design by simulation

    NASA Technical Reports Server (NTRS)

    Williams, T.; Kerner, H.; Weatherbee, J. E.; Taylor, D. S.; Hodges, B.

    1973-01-01

    A deterministic simulator is described which models the Automatically Reconfigurable Modular Multiprocessor System (ARMMS), a candidate computer system for future manned and unmanned space missions. Its use as a tool to study and determine the minimum computer system configuration necessary to satisfy the on-board computational requirements of a typical mission is presented. The paper describes how the computer system configuration is determined in order to satisfy the data processing demand of the various shuttle booster subsytems. The configuration which is developed as a result of studies with the simulator is optimal with respect to the efficient use of computer system resources.

  18. Optimum spaceborne computer system design by simulation

    NASA Technical Reports Server (NTRS)

    Williams, T.; Weatherbee, J. E.; Taylor, D. S.

    1972-01-01

    A deterministic digital simulation model is described which models the Automatically Reconfigurable Modular Multiprocessor System (ARMMS), a candidate computer system for future manned and unmanned space missions. Use of the model as a tool in configuring a minimum computer system for a typical mission is demonstrated. The configuration which is developed as a result of studies with the simulator is optimal with respect to the efficient use of computer system resources, i.e., the configuration derived is a minimal one. Other considerations such as increased reliability through the use of standby spares would be taken into account in the definition of a practical system for a given mission.

  19. Space shuttle visual simulation system design study

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The current and near-future state-of-the-art in visual simulation equipment technology is related to the requirements of the space shuttle visual system. Image source, image sensing, and displays are analyzed on a subsystem basis, and the principal conclusions are used in the formulation of a recommended baseline visual system. Perceptibility and visibility are also analyzed.

  20. RAS Interaction with PI3K

    PubMed Central

    Castellano, Esther; Downward, Julian

    2011-01-01

    RAS proteins are small GTPases known for their involvement in oncogenesis: around 25% of human tumors present mutations in a member of this family. RAS operates in a complex signaling network with multiple activators and effectors, which allows them to regulate many cellular functions such as cell proliferation, differentiation, apoptosis, and senescence. Phosphatidylinositol 3-kinase (PI3K) is one of the main effector pathways of RAS, regulating cell growth, cell cycle entry, cell survival, cytoskeleton reorganization, and metabolism. However, it is the involvement of this pathway in human tumors that has attracted most attention. PI3K has proven to be necessary for RAS-induced transformation in vitro, and more importantly, mice with mutations in the PI3K catalytic subunit p110α that block its ability to interact with RAS are highly resistant to endogenous oncogenic KRAS-induced lung tumorigenesis and HRAS-induced skin carcinogenesis. These animals also have a delayed development of the lymphatic vasculature. Many PI3K inhibitors have been developed that are now in clinical trials. However, it is a complex pathway with many feedback loops, and interactions with other pathways make the results of its inhibition hard to predict. Combined therapy with another RAS-regulated pathway such as RAF/MEK/ERK may be the most effective way to treat cancer, at least in animal models mimicking the human disease. In this review, we will summarize current knowledge about how RAS regulates one of its best-known effectors, PI3K. PMID:21779497

  1. An HLA based design of space system simulation environment

    NASA Astrophysics Data System (ADS)

    Li, Yinghua; Li, Yong; Liu, Jie

    2007-06-01

    Space system simulation is involved in many application fields, such as space remote sensing and space communication, etc. A simulation environment which can be shared by different space system simulation is needed. Two rules, called object template towing and hierarchical reusability, are proposed. Based on these two rules, the architecture, the network structure and the function structure of the simulation environment are designed. Then, the mechanism of utilizing data resources, inheriting object models and running simulation systems are also constructed. These mechanisms make the simulation objects defined in advance be easily inherited by different HLA federates, the fundamental simulation models be shared by different simulation systems. Therefore, the simulation environment is highly universal and reusable.

  2. Metabolic Dependencies in RAS-Driven Cancers.

    PubMed

    Kimmelman, Alec C

    2015-04-15

    The ability to inhibit the RAS oncogene has been the holy grail of oncology because of the critical role of this gene in a multitude of tumor types. In addition, RAS-mutant tumors are among the most aggressive and refractory to treatment. Although directly targeting the RAS oncogene has proven challenging, an alternative approach for treating RAS-driven cancers is to inhibit critical downstream events that are required for tumor maintenance. Indeed, much focus has been put on inhibiting signaling cascades downstream of RAS. Recent studies have shown that oncogenic RAS promotes a metabolic reprogramming of tumor cells, shifting them toward an anabolic metabolism necessary to produce biomass to support unconstrained proliferation. These cancers also use a diverse set of fuel sources to meet their metabolic needs and have even developed a variety of mechanisms to act as metabolic scavengers to obtain necessary metabolic substrates from both extracellular and intracellular sources. Collectively, these adaptations can create "metabolic bottlenecks" whereby tumor cells rely on particular pathways or rate-limiting metabolites. In this regard, inhibiting individual or combinations of these metabolic pathways can attenuate growth in preclinical models. Because these dependencies are tumor selective and downstream of oncogenic RAS, there is the opportunity for therapeutic intervention. Although targeting tumor metabolism is still in the early days of translation to patients, our continued advances in understanding critical metabolic adaptations in RAS-driven cancers, as well as the ability to study this altered metabolism in relevant tumor models, will accelerate the development of new therapeutic approaches. Clin Cancer Res; 21(8); 1828-34. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers." PMID:25878364

  3. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

    PubMed Central

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

    2016-01-01

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

  4. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

    PubMed

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

    2016-01-22

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

  5. Design and Test of Advanced Thermal Simulators for an Alkali Metal-Cooled Reactor Simulator

    NASA Technical Reports Server (NTRS)

    Garber, Anne E.; Dickens, Ricky E.

    2011-01-01

    The Early Flight Fission Test Facility (EFF-TF) at NASA Marshall Space Flight Center (MSFC) has as one of its primary missions the development and testing of fission reactor simulators for space applications. A key component in these simulated reactors is the thermal simulator, designed to closely mimic the form and function of a nuclear fuel pin using electric heating. Continuing effort has been made to design simple, robust, inexpensive thermal simulators that closely match the steady-state and transient performance of a nuclear fuel pin. A series of these simulators have been designed, developed, fabricated and tested individually and in a number of simulated reactor systems at the EFF-TF. The purpose of the thermal simulators developed under the Fission Surface Power (FSP) task is to ensure that non-nuclear testing can be performed at sufficiently high fidelity to allow a cost-effective qualification and acceptance strategy to be used. Prototype thermal simulator design is founded on the baseline Fission Surface Power reactor design. Recent efforts have been focused on the design, fabrication and test of a prototype thermal simulator appropriate for use in the Technology Demonstration Unit (TDU). While designing the thermal simulators described in this paper, effort were made to improve the axial power profile matching of the thermal simulators. Simultaneously, a search was conducted for graphite materials with higher resistivities than had been employed in the past. The combination of these two efforts resulted in the creation of thermal simulators with power capacities of 2300-3300 W per unit. Six of these elements were installed in a simulated core and tested in the alkali metal-cooled Fission Surface Power Primary Test Circuit (FSP-PTC) at a variety of liquid metal flow rates and temperatures. This paper documents the design of the thermal simulators, test program, and test results.

  6. Physiological Based Simulator Fidelity Design Guidance

    NASA Technical Reports Server (NTRS)

    Schnell, Thomas; Hamel, Nancy; Postnikov, Alex; Hoke, Jaclyn; McLean, Angus L. M. Thom, III

    2012-01-01

    The evolution of the role of flight simulation has reinforced assumptions in aviation that the degree of realism in a simulation system directly correlates to the training benefit, i.e., more fidelity is always better. The construct of fidelity has several dimensions, including physical fidelity, functional fidelity, and cognitive fidelity. Interaction of different fidelity dimensions has an impact on trainee immersion, presence, and transfer of training. This paper discusses research results of a recent study that investigated if physiological-based methods could be used to determine the required level of simulator fidelity. Pilots performed a relatively complex flight task consisting of mission task elements of various levels of difficulty in a fixed base flight simulator and a real fighter jet trainer aircraft. Flight runs were performed using one forward visual channel of 40 deg. field of view for the lowest level of fidelity, 120 deg. field of view for the middle level of fidelity, and unrestricted field of view and full dynamic acceleration in the real airplane. Neuro-cognitive and physiological measures were collected under these conditions using the Cognitive Avionics Tool Set (CATS) and nonlinear closed form models for workload prediction were generated based on these data for the various mission task elements. One finding of the work described herein is that simple heart rate is a relatively good predictor of cognitive workload, even for short tasks with dynamic changes in cognitive loading. Additionally, we found that models that used a wide range of physiological and neuro-cognitive measures can further boost the accuracy of the workload prediction.

  7. Optimal Living Environments for the Elderly: A Design Simulation Approach.

    ERIC Educational Resources Information Center

    Hoffman, Stephanie B.; And Others

    PLANNED AGE (Planned Alternatives for Gerontological Environments) is a consumer/advocate-oriented design simulation package that provides: (a) a medium for user-planner interaction in the design of living and service environments for the aged; (b) an educational, planning, design, and evaluation tool that can be used by the elderly, their…

  8. Object oriented simulation implementation in support of robust system design

    SciTech Connect

    Not Available

    1993-04-01

    A very brief description of two ``classes`` developed for use in design optimization and sensitivity analyses are given. These classes are used in simulations of systems in early design phases as well as system response assessments. The instanciated classes were coupled to system models to demonstrate the practically and efficiency of using these objects in complex robust design processes.

  9. JEFF: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Jeff is a remotely piloted vehicle designed by the Blue Team, a division of AE441, Inc., to fulfill the mission proposed by G-Dome Enterprises: to build a cost efficient aircraft to service Aeroworld with overnight cargo delivery. The design of Jeff was most significantly influenced by the need to minimize costs. This objective was pursued by building fewer large planes as opposed to many small planes. Thus, by building an aircraft with a large payload capacity, G-Dome Enterprises will be able to minimize the large costs and the large number of cycles that are associated with a large fleet. Another factor which had a significant influence on our design was the constraint that our design had to fit into a 2'x2'x5' storage container. This constraint meant that unless we wanted to build foldable wings that Jeff's span would be limited to 10 feet. Since this was not enough lifting surface to suit our needs a canard configuration was chosen to get the needed lifting surface and avoid the structural dilemma of foldable wings. The aircraft is constructed mainly of balsa, with spruce wing and canard spars and a monokote covering. It was designed to support a maximum payload weight of 35 oz. (total aircraft weight of 108 oz.) and withstand a maximum load factor of 2.5.

  10. Scramjet Propulsive Flowpath Design and Numerical Simulation

    NASA Astrophysics Data System (ADS)

    Li, Jian-ping; Song, Wen-yan; Liu, Xin

    2014-06-01

    The integrated propulsive flowpath of scramjet configuration was preliminarily designed and analyzed in this paper. The flow-fields characteristics and performance of the designed two-dimensional integrated propulsive flowpath were numerically calculated under various equivalent fuel-air ratio conditions, using computational fluid dynamics methods. The calculation results were then compared with the experimental data on some typical conditions, and the flow-field and performance of the integrated scramjet flowpath with different equivalent fuel-air ratios were analyzed and discussed in detail. The investigation results from these efforts showed that: (1) the inlet function was beyond disturbances by combustion induced shock wave and pressure fluctuations under the equivalent fuel-air ratio condition of 1.0, which well satisfied the design requirements; (2) with the increasing equivalent fuel-air ratio, the combustion intensity in the combustor was significantly enhanced, resulting in an increasing net-thrust of the propulsive flowpath.

  11. Dynamics of adaptive structures: Design through simulations

    NASA Technical Reports Server (NTRS)

    Park, K. C.; Alexander, S.

    1993-01-01

    The use of a helical bi-morph actuator/sensor concept by mimicking the change of helical waveform in bacterial flagella is perhaps the first application of bacterial motions (living species) to longitudinal deployment of space structures. However, no dynamical considerations were analyzed to explain the waveform change mechanisms. The objective is to review various deployment concepts from the dynamics point of view and introduce the dynamical considerations from the outset as part of design considerations. Specifically, the impact of the incorporation of the combined static mechanisms and dynamic design considerations on the deployment performance during the reconfiguration stage is studied in terms of improved controllability, maneuvering duration, and joint singularity index. It is shown that intermediate configurations during articulations play an important role for improved joint mechanisms design and overall structural deployability.

  12. Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T Cells

    PubMed Central

    Jun, Jesse E.; Rubio, Ignacio; Roose, Jeroen P.

    2013-01-01

    The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells. PMID:24027568

  13. Advanced ERS design using computer simulation

    SciTech Connect

    Melhem, G.A.

    1995-12-31

    There are two schools of thought regarding pressure relief design, shortcut/simplified methods and detailed methods. The shortcut/simplified methods are mostly applicable to non-reactive systems. These methods use direct scale-up techniques to obtain a vent size. Little useful information can be obtained for reaction data such as onset temperatures, activation energy, decompositon stoichiometry, etc. In addition, this approach does not readily provide the ability to perform what-if and sensitivity analysis or data that can be used for post-release mitigation design. The detailed approach advocates a more fundamental approach to pressure relief design, especially for reactive systems. First, the reaction chemistry is qualified using small scale experiments and then this data is coupled with fluid dynamics to design the emergency relief system. In addition to vent sizing information, this approach provides insights into process modification and refinement as well as the establishment of a safe operating envelope. This approach provides necessary flow data for vent containment design (if required), structural support, etc. This approach also allows the direct evaluation of design sensitivity to variables such as temperature, pressure, composition, fill level, etc. on vent sizing while the shortcut approach requires an additional experiment per what-if scenario. This approach meets DIERS technology requirements for two-phase flow and vapor/liquid disengagement and exceeds it in many key areas for reacting systems such as stoichiometry estimation for decomposition reactions, non-ideal solutions effects, continuing reactions in piping and vent containment systems, etc. This paper provides an overview of our proposed equation of state based modeling approach and its computer code implementation. Numerous examples and model validations are also described. 42 refs., 23 figs., 9 tabs.

  14. Robust Design of Motor PWM Control using Modeling and Simulation

    NASA Astrophysics Data System (ADS)

    Zhan, Wei

    A robust design method is developed for Pulse Width Modulation (PWM) motor speed control. A first principle model for DC permanent magnetic motor is used to build a Simulink model for simulation and analysis. Based on the simulation result, the main factors that contributed to the average speed variation are identified using Design of Experiment (DOE). A robust solution is derived to reduce the aver age speed control variation using Response Surface Method (RSM). The robustness of the new design is verified using the simulation model.

  15. Pyrometry simulator (pyrosim) for diagnostic design.

    SciTech Connect

    Dolan, Daniel H., III

    2011-10-01

    Signal estimates are crucial to the design of time-resolved pyrometry measurements. These estimates affect fundamental design decisions, including the optical relay (fiber versus open beam), spectral range (visible or infrared), and amplification needs (possibly at the expense of time resolution). The pyrosim program makes such estimates, allowing the collected power, photon flux, and measured signal to be determined in a broad range of pyrometry measurements. Geometrical collection limits can be applied; sample emissivity, transfer efficiency, and detector sensitivity may also be specified, either as constants or functions of wavelength.

  16. Designing a SCADA system simulator for fast breeder reactor

    NASA Astrophysics Data System (ADS)

    Nugraha, E.; Abdullah, A. G.; Hakim, D. L.

    2016-04-01

    SCADA (Supervisory Control and Data Acquisition) system simulator is a Human Machine Interface-based software that is able to visualize the process of a plant. This study describes the results of the process of designing a SCADA system simulator that aims to facilitate the operator in monitoring, controlling, handling the alarm, accessing historical data and historical trend in Nuclear Power Plant (NPP) type Fast Breeder Reactor (FBR). This research used simulation to simulate NPP type FBR Kalpakkam in India. This simulator was developed using Wonderware Intouch software 10 and is equipped with main menu, plant overview, area graphics, control display, set point display, alarm system, real-time trending, historical trending and security system. This simulator can properly simulate the principle of energy flow and energy conversion process on NPP type FBR. This SCADA system simulator can be used as training media for NPP type FBR prospective operators.

  17. Biochemical similarity of Schizosaccharomyces pombe ras1 protein with RAS2 protein of Saccharomyces cervisiae.

    PubMed

    Onozawa, T; Danjoh, I; Fujiyama, A

    1995-07-01

    Schizosaccharomyces pombe contains single ras oncogene homologue, ras1, that functions in the signal transduction pathway conducting the cell's mating processes. To understand the biochemical basis of yeast ras proteins, we have purified the ras1 protein and compared the major biochemical constants with those of RAS2 protein from Saccharomyces cerevisiae and mammalian ras proteins. The purified ras1 protein showed a remarkably high Kd value for GDP binding (178 nM) and for binding with ATP. In contrast, the Kd value for GTP binding and the rate of GTPase activity were 64 nM and 77 x 10(-6) s-1 at 37 degrees C, respectively; both were higher than normal p21ras protein, but at the same level as the RAS2 protein. We directly measured rate of GTP binding and GDP binding which were 3.9 x 10(-3) s-1 and 1.8 x 10(-3) s-1 at 30 degrees C, respectively. On the other hand, exchange rates between bound and free nucleotides remained almost constant throughout the tested combination of GTP and GDP, and were several-fold lower than the binding rate. These results suggest that the release of the guanine nucleotide is the rate-limiting step in the ras-GTP/GDP cycle. As a whole, the biochemical properties of the ras1 protein are close to those of the RAS2 protein, although these two proteins function differently in the signal transduction pathway in the cells. PMID:7483844

  18. Modeling and Simulation for Mission Operations Work System Design

    NASA Technical Reports Server (NTRS)

    Sierhuis, Maarten; Clancey, William J.; Seah, Chin; Trimble, Jay P.; Sims, Michael H.

    2003-01-01

    Work System analysis and design is complex and non-deterministic. In this paper we describe Brahms, a multiagent modeling and simulation environment for designing complex interactions in human-machine systems. Brahms was originally conceived as a business process design tool that simulates work practices, including social systems of work. We describe our modeling and simulation method for mission operations work systems design, based on a research case study in which we used Brahms to design mission operations for a proposed discovery mission to the Moon. We then describe the results of an actual method application project-the Brahms Mars Exploration Rover. Space mission operations are similar to operations of traditional organizations; we show that the application of Brahms for space mission operations design is relevant and transferable to other types of business processes in organizations.

  19. Simulation in the Service of Design - Asking the Right Questions

    SciTech Connect

    Donn, Michael; Selkowitz, Stephen; Bordass, Bill

    2009-03-01

    This paper proposes an approach to the creation of design tools that address the real information needs of designers in the early stages of design of nonresidential buildings. Traditional simplified design tools are typically too limited to be of much use, even in conceptual design. The proposal is to provide access to the power of detailed simulation tools, at a stage in design when little is known about the final building, but at a stage also when the freedom to explore options is greatest. The proposed approach to tool design has been derived from consultation with design analysis teams as part of the COMFEN tool development. The paper explores how tools like COMFEN have been shaped by this consultation and how requests from these teams for real-world relevance might shape such tools in the future, drawing into the simulation process the lessons from Post Occupancy Evaluation (POE) of buildings.

  20. Arrow 227: Air transport system design simulation

    NASA Technical Reports Server (NTRS)

    Bontempi, Michael; Bose, Dave; Brophy, Georgeann; Cashin, Timothy; Kanarios, Michael; Ryan, Steve; Peterson, Timothy

    1992-01-01

    The Arrow 227 is a student-designed commercial transport for use in a overnight package delivery network. The major goal of the concept was to provide the delivery service with the greatest potential return on investment. The design objectives of the Arrow 227 were based on three parameters; production cost, payload weight, and aerodynamic efficiency. Low production cost helps to reduce initial investment. Increased payload weight allows for a decrease in flight cycles and, therefore, less fuel consumption than an aircraft carrying less payload weight and requiring more flight cycles. In addition, fewer flight cycles will allow a fleet to last longer. Finally, increased aerodynamic efficiency in the form of high L/D will decrease fuel consumption.

  1. Design and simulation of an ultrasonic transducer

    NASA Astrophysics Data System (ADS)

    Yu, Zhenxian; Shi, Yanru; Hsu, Hung-Yao; Kong, Lingxue

    2005-12-01

    This paper presents a novel ultrasonic transducer which can be used as a liquid ejector to release drug. The ultrasonic transducer is based on the design of a flextensional transducer, which is composed of interdigital piezoelectric rings and a vibration membrane. The device works at an axisymmetric resonant mode to produce maximum amplitude at the center of the vibration membrane in axial direction. For the usage of multi piezoelectric rings, the flexural plate waves can be generated by applying two out-of-phase signals. The power consumption is of primary importance in the design of this device and the usage of single-ring or multi-ring piezoelectric material instead of bulk piezo material can therefore reduce the power consumption. An optimum working frequency, at which least power is required by the device, can be found by the piezoelectric, coupled field capability of the ANSYS/Multiphysics product.

  2. Design of object-oriented distributed simulation classes

    NASA Technical Reports Server (NTRS)

    Schoeffler, James D. (Principal Investigator)

    1995-01-01

    Distributed simulation of aircraft engines as part of a computer aided design package is being developed by NASA Lewis Research Center for the aircraft industry. The project is called NPSS, an acronym for 'Numerical Propulsion Simulation System'. NPSS is a flexible object-oriented simulation of aircraft engines requiring high computing speed. It is desirable to run the simulation on a distributed computer system with multiple processors executing portions of the simulation in parallel. The purpose of this research was to investigate object-oriented structures such that individual objects could be distributed. The set of classes used in the simulation must be designed to facilitate parallel computation. Since the portions of the simulation carried out in parallel are not independent of one another, there is the need for communication among the parallel executing processors which in turn implies need for their synchronization. Communication and synchronization can lead to decreased throughput as parallel processors wait for data or synchronization signals from other processors. As a result of this research, the following have been accomplished. The design and implementation of a set of simulation classes which result in a distributed simulation control program have been completed. The design is based upon MIT 'Actor' model of a concurrent object and uses 'connectors' to structure dynamic connections between simulation components. Connectors may be dynamically created according to the distribution of objects among machines at execution time without any programming changes. Measurements of the basic performance have been carried out with the result that communication overhead of the distributed design is swamped by the computation time of modules unless modules have very short execution times per iteration or time step. An analytical performance model based upon queuing network theory has been designed and implemented. Its application to realistic configurations has

  3. Design of Object-Oriented Distributed Simulation Classes

    NASA Technical Reports Server (NTRS)

    Schoeffler, James D.

    1995-01-01

    Distributed simulation of aircraft engines as part of a computer aided design package being developed by NASA Lewis Research Center for the aircraft industry. The project is called NPSS, an acronym for "Numerical Propulsion Simulation System". NPSS is a flexible object-oriented simulation of aircraft engines requiring high computing speed. It is desirable to run the simulation on a distributed computer system with multiple processors executing portions of the simulation in parallel. The purpose of this research was to investigate object-oriented structures such that individual objects could be distributed. The set of classes used in the simulation must be designed to facilitate parallel computation. Since the portions of the simulation carried out in parallel are not independent of one another, there is the need for communication among the parallel executing processors which in turn implies need for their synchronization. Communication and synchronization can lead to decreased throughput as parallel processors wait for data or synchronization signals from other processors. As a result of this research, the following have been accomplished. The design and implementation of a set of simulation classes which result in a distributed simulation control program have been completed. The design is based upon MIT "Actor" model of a concurrent object and uses "connectors" to structure dynamic connections between simulation components. Connectors may be dynamically created according to the distribution of objects among machines at execution time without any programming changes. Measurements of the basic performance have been carried out with the result that communication overhead of the distributed design is swamped by the computation time of modules unless modules have very short execution times per iteration or time step. An analytical performance model based upon queuing network theory has been designed and implemented. Its application to realistic configurations has not

  4. NAM: The 2004 RAS National Astronomy Meeting

    NASA Astrophysics Data System (ADS)

    Jones, Barrie; Norton, Andrew

    2004-06-01

    This year's RAS National Astronomy Meeting was held at the Open University's Milton Keynes campus from 29 March to 2 April. The event was organized by members of the OU Physics & Astronomy Department and Planetary & Space Science Research Institute. Around 450 people attended the meeting, at which more than 220 talks were presented, along with around 90 posters. Co-chairs of RAS NAM04, Barrie Jones and Andrew Norton, summarize.

  5. Hypervelocity impact simulation for micrometeorite and debris shield design

    NASA Technical Reports Server (NTRS)

    Fahrenthold, Eric P.

    1992-01-01

    A new capability has been developed for direct computer simulation of hypervelocity impacts on multi-plate orbital debris shields, for combinations of low shield thickness and wide shield spacing which place extreme demands on conventional Eulerian analysis techniques. The modeling methodology represents a novel approach to debris cloud dynamics simulation, a problem of long term interest in the design of space structures. Software implementation of the modeling methodology provides a new design tool for engineering analysis of proposed orbital debris protection systems.

  6. The Design, Development, and Evaluation of an Evaluative Computer Simulation.

    ERIC Educational Resources Information Center

    Ehrlich, Lisa R.

    This paper discusses evaluation design considerations for a computer based evaluation simulation developed at the University of Iowa College of Medicine in Cardiology to assess the diagnostic skills of primary care physicians and medical students. The simulation developed allows for the assessment of diagnostic skills of physicians in the…

  7. Design Model for Learner-Centered, Computer-Based Simulations.

    ERIC Educational Resources Information Center

    Hawley, Chandra L.; Duffy, Thomas M.

    This paper presents a model for designing computer-based simulation environments within a constructivist framework for the K-12 school setting. The following primary criteria for the development of simulations are proposed: (1) the problem needs to be authentic; (2) the cognitive demand in learning should be authentic; (3) scaffolding supports a…

  8. Inhibition of RAS in diabetic nephropathy

    PubMed Central

    Yacoub, Rabi; Campbell, Kirk N

    2015-01-01

    Diabetic kidney disease (DKD) is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS) is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII), the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population. PMID:25926752

  9. Effectively design and simulate thermosyphon reboiler systems. Part 1

    SciTech Connect

    Martin, G.R.; Sloley, A.W.

    1995-06-01

    Thermosyphon reboilers provide a simple, low-maintenance design for distillation tower reboiler systems. With an understanding of all the factors involved, thermosyphon designs should be more reliable than most other reboiler systems due to an absence of moving parts (pumps) in the process circulation loop. Design of true thermosyphon exchangers requires an intimate knowledge of a distillation tower`s heat balance, temperature levels and pressure balance in there boiler loop. Temperature levels vary strongly with composition gradients depending on the system relative volatilities. Case studies of two industrial units demonstrate implications on exchanger design of the correct and incorrect simulation configuration. The two cases compare a low relative-volatility {alpha} system (ethylene-ethane splitter) and a high {alpha} system (FCCU deethanizer). Main factors include impact on equipment size and design. Proper design criteria for thermosyphon exchanger and distillation tower simulation and for integrating process and equipment design are also shown.

  10. ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells

    PubMed Central

    Wang, Y; Godin-Heymann, N; Dan Wang, X; Bergamaschi, D; Llanos, S; Lu, X

    2013-01-01

    RAS mutations occur frequently in human cancer and activated RAS signalling contributes to tumour development and progression. Apart from its oncogenic effects on cell growth, active RAS has tumour-suppressive functions via its ability to induce cellular senescence and apoptosis. RAS is known to induce p53-dependent cell cycle arrest, yet its effect on p53-dependent apoptosis remains unclear. We report here that apoptosis-stimulating protein of p53 (ASPP) 1 and 2, two activators of p53, preferentially bind active RAS via their N-terminal RAS-association domains (RAD). Additionally, ASPP2 colocalises with and contributes to RAS cellular membrane localisation and potentiates RAS signalling. In cancer cells, ASPP1 and ASPP2 cooperate with oncogenic RAS to enhance the transcription and apoptotic function of p53. Thus, loss of ASPP1 and ASPP2 in human cancer cells may contribute to the full transforming property of RAS oncogene. PMID:23392125

  11. Design Factors for Educationally Effective Animations and Simulations

    ERIC Educational Resources Information Center

    Plass, Jan L.; Homer, Bruce D.; Hayward, Elizabeth O.

    2009-01-01

    This paper reviews research on learning from dynamic visual representations and offers principles for the design of animations and simulations that assure their educational effectiveness. In addition to established principles, new and revised design principle are presented that have been derived from recent research. Our review focuses on the…

  12. Simulations Using a Computer/Videodisc System: Instructional Design Considerations.

    ERIC Educational Resources Information Center

    Ehrlich, Lisa R.

    Instructional design considerations involved in using level four videodisc systems when designing simulations are explored. Discussion of the hardware and software system characteristics notes that computer based training offers the features of text, graphics, color, animation, and highlighting techniques, while a videodisc player offers all of…

  13. Advanced Simulation and Computing Co-Design Strategy

    SciTech Connect

    Ang, James A.; Hoang, Thuc T.; Kelly, Suzanne M.; McPherson, Allen; Neely, Rob

    2015-11-01

    This ASC Co-design Strategy lays out the full continuum and components of the co-design process, based on what we have experienced thus far and what we wish to do more in the future to meet the program’s mission of providing high performance computing (HPC) and simulation capabilities for NNSA to carry out its stockpile stewardship responsibility.

  14. Design by Dragging: An Interface for Creative Forward and Inverse Design with Simulation Ensembles

    PubMed Central

    Coffey, Dane; Lin, Chi-Lun; Erdman, Arthur G.; Keefe, Daniel F.

    2014-01-01

    We present an interface for exploring large design spaces as encountered in simulation-based engineering, design of visual effects, and other tasks that require tuning parameters of computationally-intensive simulations and visually evaluating results. The goal is to enable a style of design with simulations that feels as-direct-as-possible so users can concentrate on creative design tasks. The approach integrates forward design via direct manipulation of simulation inputs (e.g., geometric properties, applied forces) in the same visual space with inverse design via “tugging” and reshaping simulation outputs (e.g., scalar fields from finite element analysis (FEA) or computational fluid dynamics (CFD)). The interface includes algorithms for interpreting the intent of users’ drag operations relative to parameterized models, morphing arbitrary scalar fields output from FEA and CFD simulations, and in-place interactive ensemble visualization. The inverse design strategy can be extended to use multi-touch input in combination with an as-rigid-as-possible shape manipulation to support rich visual queries. The potential of this new design approach is confirmed via two applications: medical device engineering of a vacuum-assisted biopsy device and visual effects design using a physically based flame simulation. PMID:24051845

  15. Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

    PubMed Central

    Coyle, Scott M; Lim, Wendell A

    2016-01-01

    The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras’s ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease. DOI: http://dx.doi.org/10.7554/eLife.12435.001 PMID:26765565

  16. Binding hotspots on K-Ras: consensus ligand binding sites and other reactive regions from probe-based molecular dynamics analysis

    PubMed Central

    Prakash, Priyanka; Hancock, John F.; Gorfe, Alemayehu A.

    2015-01-01

    We have used probe-based molecular dynamics (pMD) simulations to search for interaction hotspots on the surface of the therapeutically highly relevant oncogenic K-Ras G12D. Combining the probe-based query with an ensemble-based pocket identification scheme and an analysis of existing Ras-ligand complexes, we show that (i) pMD is a robust and cost-effective strategy for binding site identification, (ii) all four of the previously reported ligand binding sites are suitable for structure-based ligand design, and (iii) in some cases probe binding and expanded sampling of configurational space enable pocket expansion and increase the likelihood of site identification. Furthermore, by comparing the distribution of hotspots in non-pocket-like regions with known protein- and membrane-interacting interfaces, we propose that pMD has the potential to predict surface patches responsible for protein-biomolecule interactions. These observations have important implications for future drug design efforts and will facilitate the search for potential interfaces responsible for the proposed transient oligomerization or interaction of Ras with other biomolecules in the cellular milieu. PMID:25740554

  17. Evolutionary Design and Simulation of a Tube Crawling Inspection Robot

    NASA Technical Reports Server (NTRS)

    Craft, Michael; Howsman, Tom; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

    2002-01-01

    The Space Robotics Assembly Team Simulation (SpaceRATS) is an expansive concept that will hopefully lead to a space flight demonstration of a robotic team cooperatively assembling a system from its constitutive parts. A primary objective of the SpaceRATS project is to develop a generalized evolutionary design approach for multiple classes of robots. The portion of the overall SpaceRats program associated with the evolutionary design and simulation of an inspection robot's morphology is the subject of this paper. The vast majority of this effort has concentrated on the use and modification of Darwin2K, a robotic design and simulation software package, to analyze the design of a tube crawling robot. This robot is designed for carrying out inspection duties in relatively inaccessible locations within a liquid rocket engine similar to the SSME. A preliminary design of the tube crawler robot was completed, and the mechanical dynamics of the system were simulated. An evolutionary approach to optimizing a few parameters of the system was utilized, resulting in a more optimum design.

  18. Activated K-Ras, But Not H-Ras or N-Ras, Regulates Brain Neural Stem Cell Proliferation in a Raf/Rb-Dependent Manner

    PubMed Central

    Bender, R. Hugh F.; Haigis, Kevin M.; Gutmann, David H.

    2016-01-01

    Neural stem cells (NSCs) give rise to all the major cell types in the brain, including neurons, oligodendrocytes, and astrocytes. However, the intracellular signaling pathways that govern brain NSC proliferation and differentiation have been incompletely characterized to date. Since some neurodevelopmental brain disorders (Costello syndrome and Noonan syndrome) are caused by germline activating mutations in the RAS genes, Ras small GTPases are likely critical regulators of brain NSC function. In the mammalian brain, Ras exists as three distinct molecules (H-Ras, K-Ras, and N-Ras), each with different subcellular localizations, downstream signaling effectors, and biological effects. Leveraging a novel series of conditional-activated Ras molecule-expressing genetically engineered mouse strains, we demonstrate that activated K-Ras, but not H-Ras or N-Ras, expression increases brain NSC growth in a Raf-dependent, but Mek-independent, manner. Moreover, we show that activated K-Ras regulation of brain NSC proliferation requires Raf binding and suppression of retinoblastoma (Rb) function. Collectively, these observations establish tissue-specific differences in activated Ras molecule regulation of brain cell growth that operate through a noncanonical mechanism. PMID:25788415

  19. Past, Present, and Future of Targeting Ras for Cancer Therapies.

    PubMed

    Tan, Zhi; Zhang, Shuxing

    2016-01-01

    For decades, mutant Ras (mut-Ras) proteins have been identified as drivers of multiple cancers including pancreatic, lung, and colon cancers. However, targeting this oncogene has been challenging and no Ras inhibitors are on the market to date. Lately several candidates targeting the downstream pathways of Ras signaling, including PI3K and Raf, were approved for cancer treatment. However, they do not present promising therapeutic effects on patients harboring Ras mutations. Recently, a variety of compounds have been reported to impair the activity of Ras, and these exciting discoveries reignite the hope for development of novel drugs targeting mut-Ras. In this article, we will review the progress made in this field and the current state-of-the-art technologies to develop Ras inhibitors. Also we will discuss the future direction of targeting Ras. PMID:26423695

  20. RasGRP1 and RasGRP3 Are Required for Efficient Generation of Early Thymic Progenitors.

    PubMed

    Golec, Dominic P; Henao Caviedes, Laura M; Baldwin, Troy A

    2016-09-01

    T cell development is dependent on the migration of progenitor cells from the bone marrow to the thymus. Upon reaching the thymus, progenitors undergo a complex developmental program that requires inputs from various highly conserved signaling pathways including the Notch and Wnt pathways. To date, Ras signaling has not been implicated in the very earliest stages of T cell differentiation, but members of a family of Ras activators called RasGRPs have been shown to be involved at multiple stages of T cell development. We examined early T cell development in mice lacking RasGRP1, RasGRP3, and RasGRPs 1 and 3. We report that RasGRP1- and RasGRP3-deficient thymi show significantly reduced numbers of early thymic progenitors (ETPs) relative to wild type thymi. Furthermore, RasGRP1/3 double-deficient thymi show significant reductions in ETP numbers compared with either RasGRP1 or RasGRP3 single-deficient thymi, suggesting that both RasGRP1 and RasGRP3 regulate the generation of ETPs. In addition, competitive bone marrow chimera experiments reveal that RasGRP1/3 double-deficient progenitors intrinsically generate ETPs less efficiently than wild type progenitors. Finally, RasGRP1/3-deficient progenitors show impaired migration toward the CCR9 ligand, CCL25, suggesting that RasGRP1 and RasGRP3 may regulate progenitor entry into the thymus through a CCR9-dependent mechanism. These data demonstrate that, in addition to Notch and Wnt, the highly conserved Ras pathway is critical for the earliest stages of T cell development and further highlight the importance of Ras signaling during thymocyte maturation. PMID:27465532

  1. Design, simulation, evaluation, and technological verification of arrayed waveguide gratings

    NASA Astrophysics Data System (ADS)

    Seyringer, Dana; Schmid, Patrick; Bielik, Michal; Uherek, Frantisek; Chovan, Jozef; Kuzma, Anton

    2014-07-01

    We present the design, simulation, evaluation, and technological verification of various low-index optical demultiplexers based on arrayed waveguide gratings (AWGs). When designing such optical demultiplexers, a set of input geometrical parameters must be first calculated. They are essential to create AWG layout that will be then simulated using commercial photonics tools. However, these tools do not support or support only partially such a fundamental calculation. Therefore, a new stand-alone tool called AWG-Parameters was developed, which strongly reduces the time needed for the design. From the calculated geometrical parameters, the AWG layouts were created and simulated using three commercial photonic tools: Optiwave, (Ottawa, Ontario, Canada), Apollo Photonics, (Ancaster, Ontario, Canada), and R-Soft, (Pasadena, California). The designs were also technologically verified. The simulated/measured transmission characteristics were evaluated by our newly developed AWG-Analyzer tool. This tool provides calculations of AWG transmission parameters, which are also missing in commercial photonic tools. Additionally, the tool provides clear definitions of calculated transmission parameters together with their textual and graphical representations. Finally, the transmission characteristics and parameters achieved from different photonic tools were compared with each other and discussed in detail. The simulated results were also compared with the measurements. Very good agreement was achieved between theoretical (AWG-Parameters tool), simulated (commercial photonic tools), and fabricated AWG transmission parameters.

  2. Ras Conformational Ensembles, Allostery, and Signaling.

    PubMed

    Lu, Shaoyong; Jang, Hyunbum; Muratcioglu, Serena; Gursoy, Attila; Keskin, Ozlem; Nussinov, Ruth; Zhang, Jian

    2016-06-01

    Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational ensembles and the allosteric regulation of Ras proteins and their interpretation from our conformational landscape standpoint. The Ras ensemble embodies all states, including the ligand-bound conformations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, transition states, and nonfunctional states serving as a reservoir for emerging functions. The ensemble is shifted by distinct mutational events, cofactors, post-translational modifications, and different membrane compositions. A better understanding of Ras biology can contribute to therapeutic strategies. PMID:26815308

  3. Biologically-inspired hexapod robot design and simulation

    NASA Technical Reports Server (NTRS)

    Espenschied, Kenneth S.; Quinn, Roger D.

    1994-01-01

    The design and construction of a biologically-inspired hexapod robot is presented. A previously developed simulation is modified to include models of the DC drive motors, the motor driver circuits and their transmissions. The application of this simulation to the design and development of the robot is discussed. The mechanisms thought to be responsible for the leg coordination of the walking stick insect were previously applied to control the straight-line locomotion of a robot. We generalized these rules for a robot walking on a plane. This biologically-inspired control strategy is used to control the robot in simulation. Numerical results show that the general body motion and performance of the simulated robot is similar to that of the robot based on our preliminary experimental results.

  4. Vestibular models for design and evaluation of flight simulator motion

    NASA Technical Reports Server (NTRS)

    Bussolari, S. R.; Sullivan, R. B.; Young, L. R.

    1986-01-01

    The use of spatial orientation models in the design and evaluation of control systems for motion-base flight simulators is investigated experimentally. The development of a high-fidelity motion drive controller using an optimal control approach based on human vestibular models is described. The formulation and implementation of the optimal washout system are discussed. The effectiveness of the motion washout system was evaluated by studying the response of six motion washout systems to the NASA/AMES Vertical Motion Simulator for a single dash-quick-stop maneuver. The effects of the motion washout system on pilot performance and simulator acceptability are examined. The data reveal that human spatial orientation models are useful for the design and evaluation of flight simulator motion fidelity.

  5. RasGRP3, a Ras activator, contributes to signaling and the tumorigenic phenotype in human melanoma

    PubMed Central

    Li, Luowei; Kedei, Noemi; Tóth, Zsuzsanna E.; Czap, Alexandra; Velasquez, Julia F.; Mihova, Daniela; Michalowski, Aleksandra M.; Yuspa, Stuart H.; Blumberg, Peter M.

    2014-01-01

    RasGRP3, an activator for H-Ras, R-Ras and Rap1/2, has emerged as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. Here, we report that RasGRP3 showed a high level of expression in multiple human melanoma cell lines as well as in a subset of human melanoma tissue samples. Suppression of endogenous RasGRP3 expression in these melanoma cell lines reduced Ras-GTP formation as well as c-Met expression and Akt phosphorylation downstream from HGF or EGF stimulation. RasGRP3 suppression also inhibited cell proliferation and reduced both colony formation in soft agar and xenograft tumor growth in immunodeficient mice, demonstrating the importance of RasGRP3 for the transformed phenotype of the melanoma cells. Reciprocally, overexpression of RasGRP3 in human primary melanocytes altered cellular morphology, markedly enhanced cell proliferation, and rendered the cells tumorigenic in a mouse xenograft model. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses and suppressed cell growth, confirming the functional role of RasGRP3 in the altered behavior of these cells. The identification of the role of RasGRP3 in melanoma highlights its importance, as a Ras activator, in the phosphoinositide signaling pathway in human melanoma and provides a new potential therapeutic target. PMID:21602881

  6. Specific repression of mutant K-RAS by 10-23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies

    SciTech Connect

    Yu, S.-H.; Wang, T.-H.; Au, L.-C.

    2009-01-09

    Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10-23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine-pyrimidine dinucleotide. Taking advantage of this specific property, 10-23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU {yields} GUU) at the GU dinucleotide while left the wild-type (WT) K-Ras mRNA intact. The K-Ras(G12V)-specific 10-23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10-23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.

  7. Basal but not luminal mammary epithelial cells require PI3K/mTOR signaling for Ras-driven overgrowth.

    PubMed

    Plichta, Kristin A; Mathers, Jessica L; Gestl, Shelley A; Glick, Adam B; Gunther, Edward J

    2012-11-15

    The mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V) together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor-initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia. PMID:23010075

  8. LEGO - A Class Library for Accelerator Design and Simulation

    SciTech Connect

    Cai, Yunhai

    1998-11-19

    An object-oriented class library of accelerator design and simulation is designed and implemented in a simple and modular fashion. All physics of single-particle dynamics is implemented based on the Hamiltonian in the local frame of the component. Symplectic integrators are used to approximate the integration of the Hamiltonian. A differential algebra class is introduced to extract a Taylor map up to arbitrary order. Analysis of optics is done in the same way both for the linear and non-linear cases. Recently, Monte Carlo simulation of synchrotron radiation has been added into the library. The code is used to design and simulate the lattices of the PEP-II and SPEAR3. And it is also used for the commissioning of the PEP-II. Some examples of how to use the library will be given.

  9. Simulation system architecture design for generic communications link

    NASA Technical Reports Server (NTRS)

    Tsang, Chit-Sang; Ratliff, Jim

    1986-01-01

    This paper addresses a computer simulation system architecture design for generic digital communications systems. It addresses the issues of an overall system architecture in order to achieve a user-friendly, efficient, and yet easily implementable simulation system. The system block diagram and its individual functional components are described in detail. Software implementation is discussed with the VAX/VMS operating system used as a target environment.

  10. New tools for the simulation and design of calorimeters

    SciTech Connect

    Womersley, W.J.

    1989-07-10

    Two new approaches to the simulation and design of large hermetic calorimeters are presented. Firstly, the Shower Library scheme used in the fast generation of showers in the Monte Carlo of the calorimeter for the D-Zero experiment at the Fermilab Tevatron is described. Secondly, a tool for the design future calorimeters is described, which can be integrated with a computer aided design system to give engineering designers an immediate idea of the relative physics capabilities of different geometries. 9 refs., 6 figs., 1 tab.

  11. Designing and implementing full immersion simulation as a research tool.

    PubMed

    Munroe, Belinda; Buckley, Thomas; Curtis, Kate; Morris, Richard

    2016-05-01

    Simulation is a valuable research tool used to evaluate the clinical performance of devices, people and systems. The simulated setting may address concerns unique to complex clinical environments such as the Emergency Department, which make the conduct of research challenging. There is limited evidence available to inform the development of simulated clinical scenarios for the purpose of evaluating practice in research studies, with the majority of literature focused on designing simulated clinical scenarios for education and training. Distinct differences exist in scenario design when implemented in education compared with use in clinical research studies. Simulated scenarios used to assess practice in clinical research must not comprise of any purposeful or planned teaching and be developed with a high degree of validity and reliability. A new scenario design template was devised to develop two standardised simulated clinical scenarios for the evaluation of a new assessment framework for emergency nurses. The scenario development and validation processes undertaken are described and provide an evidence-informed guide to scenario development for future clinical research studies. PMID:26917415

  12. Software Design for Interactive Graphic Radiation Treatment Simulation Systems*

    PubMed Central

    Kalet, Ira J.; Sweeney, Christine; Jacky, Jonathan

    1990-01-01

    We examine issues in the design of interactive computer graphic simulation programs for radiation treatment planning (RTP), as well as expert system programs that automate parts of the RTP process, in light of ten years of experience at designing, building and using such programs. An experiment in object-oriented design using standard Pascal shows that while some advantage is gained from the design, it is still difficult to achieve modularity and to integrate expert system components. A new design based on the Common LISP Object System (CLOS) is described. This series of designs for RTP software shows that this application benefits in specific ways from object-oriented design methods and appropriate languages and tools.

  13. Using simulation to design a central sterilization department.

    PubMed

    Lin, Feng; Lawley, Mark; Spry, Charlie; McCarthy, Kelly; Coyle-Rogers, Patricia G; Yih, Yuehwern

    2008-10-01

    A simulation project was performed to assist with redesign of the surgery department of a large tertiary hospital and to help administrators make the best decisions about relocating, staffing, and equipping the central sterilization department. A simulation model was created to analyze department configurations, staff schedules, equipment capacities, and cart-washing requirements. Performance measures examined include tray turnaround time, surgery-delay rate, and work-in-process levels. The analysis provides significant insight into how the proposed system will perform, allowing planning for expected patient volume increases. This work illustrates how simulation can facilitate the design of a central sterilization department and improve surgical sterilization operations. PMID:18928959

  14. MLS, a magnetic logic simulator for magnetic bubble logic design

    NASA Astrophysics Data System (ADS)

    Kinsman, Thomas B.; Cendes, Zoltan J.

    1987-04-01

    A computer program that simulates the logic functions of magnetic bubble devices has been developed. The program uses a color graphics screen to display the locations of bubbles on a chip during operation. It complements the simulator previously developed for modeling bubble devices on the gate level [Smith et al., IEEE Trans. Magn. MAG-19, 1835 (1983); Smith and Kryder, ibid. MAG-21, 1779 (1985)]. This new tool simplifies the design and testing of bubble logic devices, and facilitates the development of complicated LSI bubble circuits. The program operation is demonstrated with the design of an in-stream faulty loop compensator using bubble logic.

  15. An Integrated Approach for Entry Mission Design and Flight Simulations

    NASA Technical Reports Server (NTRS)

    Lu, Ping; Rao, Prabhakara

    2004-01-01

    An integrated approach for entry trajectory design, guidance, and simulation is proposed. The key ingredients for this approach are an on-line 3 degree-of-freedom entry trajectory planning algorithm and the entry guidance algorithm that generates the guidance gains automatically. When fully developed, such a tool could enable end-bend entry mission design and simulations in 3DOF and 6DOF mode from de-orbit burn to the TAEM interface and beyond, all in one key stroke. Some preliminary examples of such a capability are presented in this paper that demonstrate the potential of this type of integrated environment.

  16. SCALED SIMULATION DESIGN OF HIGH QUALITY LASER WAKEFIELD ACCELERATOR STAGES

    SciTech Connect

    Geddes, C.G.R.; Cormier-Michel, E.; Esarey, E.; Schroeder, C.B.; Leemans, W.P.; Bruhwiler, D.L.; Cowan, B.; Nieter, C.; Paul, K.; Cary, J.R.

    2009-05-04

    Design of efficient, high gradient laser driven wakefield accelerator (LWFA) stages using explicit particle-incell simulations with physical parameters scaled by plasma density is presented. LWFAs produce few percent energy spread electron bunches at 0.1-1 GeV with high accelerating gradients. Design tools are now required to predict and improve performance and efficiency of future LWFA stages. Scaling physical parameters extends the reach of explicit simulations to address applications including 10 GeV stages and stages for radiation sources, and accurately resolves deep laser depletion to evaluate efficient stages.

  17. Design and simulation challenges for FERMI@elettra

    NASA Astrophysics Data System (ADS)

    Di Mitri, S.; Allaria, E.; Badano, L.; Bontoiu, C.; Cornacchia, M.; Craievich, P.; Danailov, M.; De Ninno, G.; Diviacco, B.; Ferrando, O.; Ferry, S.; Iazzourene, F.; Milton, S. V.; Penco, G.; Spampinati, S.; Trovo', M.; Veronese, M.; Fawley, W.; Lidia, S.; Penn, G.; Qiang, J.; Sonnad, K. G.; Venturini, M.; Warnock, R.; Zholents, A. A.; Pogorelov, I. V.; Borland, M.; Bassi, G.; Ellison, J. A.; Heinemann, K.; Fiorito, R.; Shkvarunets, A.; Tobin, J. C.

    2009-09-01

    FERMI@elettra is a fourth-generation light source user facility under construction at the Elettra Laboratory in Trieste, Italy. The high-quality 1.2 GeV electron beam drives two-seeded Free Electron Lasers (FELs) in the wavelength range 100-10 nm. Wavelength tunability, variable polarization and higher electron beam energies to reach even shorter output wavelengths are also in the machine delivery plan. This paper describes the physics processes that have been modelled to simulate FERMI@elettra and the computer codes used to optimize the machine design. The paper focuses on several design challenges and how these translate into modelling and simulation challenges.

  18. An R package for simulation experiments evaluating clinical trial designs.

    PubMed

    Wang, Yuanyuan; Day, Roger

    2010-01-01

    This paper presents an open-source application for evaluating competing clinical trial (CT) designs using simulations. The S4 system of classes and methods is utilized. Using object-oriented programming provides extensibility through careful, clear interface specification; using R, an open-source widely-used statistical language, makes the application extendible by the people who design CTs: biostatisticians. Four key classes define the specifications of the population models, CT designs, outcome models and evaluation criteria. Five key methods define the interfaces for generating patient baseline characteristics, stopping rule, assigning treatment, generating patient outcomes and calculating the criteria. Documentation of their connections with the user input screens, with the central simulation loop, and with each other faciliates the extensibility. New subclasses and instances of existing classes meeting these interfaces can integrate immediately into the application. To illustrate the application, we evaluate the effect of patient pharmacokinetic heterogeneity on the performance of a common Phase I "3+3" design. PMID:21347151

  19. RAS Symposium Draws Hundreds of Attendees | Poster

    Cancer.gov

    They call themselves “rasologists”: scientists who study the RAS family of genes and the cancers that can arise due to mutations within them. This field of research is at the heart of some sobering numbers. Almost a third of all human cancers, including 95 percent of pancreatic cancers, are driven by mutated RAS genes. The American Cancer Society estimates there were 48,960 new cases of pancreatic cancer in the United States in 2015 and 40,560 deaths from the disease.

  20. Technology, design, simulation, and evaluation for SEP-hardened circuits

    NASA Technical Reports Server (NTRS)

    Adams, J. R.; Allred, D.; Barry, M.; Rudeck, P.; Woodruff, R.; Hoekstra, J.; Gardner, H.

    1991-01-01

    This paper describes the technology, design, simulation, and evaluation for improvement of the Single Event Phenomena (SEP) hardness of gate-array and SRAM cells. Through the use of design and processing techniques, it is possible to achieve an SEP error rate less than 1.0 x 10(exp -10) errors/bit-day for a 9O percent worst-case geosynchronous orbit environment.

  1. Design of a neural network simulator on a transputer array

    NASA Technical Reports Server (NTRS)

    Mcintire, Gary; Villarreal, James; Baffes, Paul; Rua, Monica

    1987-01-01

    A brief summary of neural networks is presented which concentrates on the design constraints imposed. Major design issues are discussed together with analysis methods and the chosen solutions. Although the system will be capable of running on most transputer architectures, it currently is being implemented on a 40-transputer system connected to a toroidal architecture. Predictions show a performance level equivalent to that of a highly optimized simulator running on the SX-2 supercomputer.

  2. Design and validation of a simulator for equine joint injections.

    PubMed

    Fox, Victoria; Sinclair, Charlotte; Bolt, David M; Lowe, John; Weller, Renate

    2013-01-01

    Joint injections are commonly used in equine practice for diagnosis and treatment of joint disorders. Performing joint injections is hence an essential skill for equine practitioners. However, opportunities for veterinary students to practice this skill are often scarce in veterinary curricula. The aim of this study was to design and validate an equine joint injection simulator. We hypothesized that the simulator will enhance student ability and confidence in performing joint injections. The simulator was constructed around an equine forelimb skeleton with soft tissues rebuilt using building foam and rubber bands. An electrical circuit including a buzzer, a battery, wire wool in the joints, and a hypodermic needle at the end of the cable was incorporated. If the students placed the needle into the joint correctly, instant auditory feedback was provided by the buzzer. To validate the simulator, 45 veterinary students were allocated to three groups: cadaver limb, textbook, or simulator. Students' ability to perform joint injections was tested and students' opinions were evaluated with a questionnaire. The proportion of students performing a metacarpophalangeal (MCP) joint injection correctly was significantly higher in the cadaver (93%) and simulator (76%) groups compared to the textbook group (50%). There was no significant difference between groups for performing a distal interphalangeal (DIP) joint injection correctly. Students rated the learning experience with the cadaver and simulator group high and with the textbook group low. The joint injection simulator represents an affordable teaching aid that allows students to repeatedly practice this skill in their own time with immediate feedback. PMID:23709111

  3. Conserved electrostatic fields at the Ras-effector interface measured through vibrational Stark effect spectroscopy explain the difference in tilt angle in the Ras binding domains of Raf and RalGDS.

    PubMed

    Walker, David M; Wang, Ruifei; Webb, Lauren J

    2014-10-01

    Vibrational Stark effect (VSE) spectroscopy was used to measure the electrostatic fields present at the interface of the human guanosine triphosphatase (GTPase) Ras docked with the Ras binding domain (RBD) of the protein kinase Raf. Nine amino acids located on the surface of Raf were selected for labeling with a nitrile vibrational probe. Eight of the probe locations were situated along the interface of Ras and Raf, and one probe was 2 nm away on the opposite side of Raf. Vibrational frequencies of the nine Raf nitrile probes were compared both in the monomeric, solvated protein and when docked with wild-type (WT) Ras to construct a comprehensive VSE map of the Ras-Raf interface. Molecular dynamics (MD) simulations employing an umbrella sampling strategy were used to generate a Boltzmann-weighted ensemble of nitrile positions in both the monomeric and docked complexes to determine the effect that docking has on probe location and orientation and to aid in the interpretation of VSE results. These results were compared to an identical study that was previously conducted on nine nitrile probes on the RBD of Ral guanidine dissociation stimulator (RalGDS) to make comparisons between the docked complexes formed when either of the two effectors bind to WT Ras. This comparison finds that there are three regions of conserved electrostatic fields that are formed upon docking of WT Ras with both downstream effectors. Conservation of this pattern in the docked complex then results in different binding orientations observed in otherwise structurally similar proteins. This work supports an electrostatic cause of the known binding tilt angle between the Ras-Raf and Ras-RalGDS complexes. PMID:25127074

  4. RAS Projects at the NCI Frederick National Lab

    Cancer.gov

    The RAS Initiative involves a number of projects focusing on ways to inhibit the proliferation of cancer cells by mutant RAS proteins. Projects are conducted at the FNLCR hub, with collaboration from the research community nationwide.

  5. The RAS Problem: Turning Off a Broken Switch

    Cancer.gov

    The RAS gene is commonly mutated in cancer and researchers are working to better understand how to develop drugs that can target the RAS protein, which for many years has been considered to be “undruggable.”

  6. Visible Light Communication Physical Layer Design for Jist Simulation

    NASA Astrophysics Data System (ADS)

    Tomaš, Boris

    2014-12-01

    Current advances in computer networking consider using visible light spectrum to encode and decode digital data. This approach is relatively non expensive. However, designing appropriate MAC or any other upper layer protocol for Visible Light Communication (VLC) requires appropriate hardware. This paper proposes and implements such hardware simulation (physical layer) that is compatible with existing network stack.

  7. Simulation, design, and analysis of azeotropic distillation operations

    SciTech Connect

    Bossen, B.S.; Joergensen, S.B.; Gani, R. )

    1993-04-01

    The computational tools needed for simulation, design, and analysis of azeotropic distillation operations are described. These tools include simple methods to identify the existence of binary and ternary azeotropes and to classify ternary mixtures as homogeneous or heterogeneous. The tools also include more complex methods to compute the phase diagram (or a heterogeneous liquid boiling surface), predict liquid-vapor phase equilibrium, and/or predict liquid-liquid-vapor phase equilibrium for simulations of batch and continuous distillation column operations. Important new features of these tools are the incorporation of a fast and efficient method for test of phase stability in simulation of distillation operations, the ability to handle a large range of mixtures (including mixtures with supercritical compounds), and the ability for computations covering wide ranges of temperature and pressure. On the basis of these tools, simple and consistent design algorithms are developed. The applicability of the design algorithms is verified through process simulation and analysis of the predicted behavior and data from the open literature. Conditions are given for examples illustrating (when and how possible distillation boundaries can be crossed) how multiple steady states can be obtained. Finally, the effect of changes in operating on the dynamic behavior of the azeotropic distillation columns and the sensitivity of design to the prediction of phase equilibria are presented.

  8. The design and development of a finger joint simulator.

    PubMed

    Joyce, Thomas J

    2016-05-01

    Artificial finger joints lack the long-term clinical success seen with hip and knee prostheses. In part, this can be explained by the challenges of rheumatoid arthritis, a progressive disease which attacks surrounding tissues as well as the joint itself. Therefore, the natural finger joints' biomechanics are adversely affected, and consequently, this imbalance due to subluxing forces further challenges any prosthesis. Many different designs of finger prosthesis have been offered over a period of greater than 50 years. Most of these designs have failed, and it is likely that many of these failures could have been identified had the prostheses been appropriately tested prior to implantation into patients. While finger joint simulators have been designed, arguably only those from a single centre have been able to reproduce clinical-type failures of the finger prostheses tested in them. This article describes the design and development of a finger simulator at Durham University, UK. It explains and justifies the engineering decisions made and thus the evolution of the finger simulator. In vitro results and their linkage to clinical-type failures are outlined to help to show the effectiveness of the simulator. Failures of finger implants in vivo continue to occur, and the need for appropriate in vitro testing of finger prostheses remains strong. PMID:26833697

  9. Numerical simulation and design of a thermionic electron gun

    NASA Astrophysics Data System (ADS)

    Hoseinzade, M.; Nijatie, M.; Sadighzadeh, A.

    2016-05-01

    This paper reports the simulation of an electron gun. The effects on the beam quality of some parameters on the beam quality were studied and optimal choices were identified. It gives numerical beam qualities for a common electrostatic triode gun, and the dependencies on design parameters such as electrode geometries and bias voltages to these electrodes are shown. An electron beam of diameter 5 mm with energy of 5 keV was assumed for the simulation process. Some design parameters were identified as variable parameters in the presence of space charge. These parameters are the inclination angle of emission electrode, the applied voltage to the focusing electrode, the gap width between the emission electrode and the focusing electrode and the diameter of the focusing electrode. The triode extraction system is designed and optimized by using CST software (for Particle Beam Simulations). The physical design of the extraction system is given in this paper. From the simulation results, it is concluded that the inclination angle of the emission electrode is optimized at 22.5°, the applied voltage to the focusing electrode was optimized and found to be V foc = ‑600 V, the optimal separation distance (gap between emission electrode and focusing electrode) is 4 mm, and the optimal diameter of the emission electrode is 14 mm. Initial results for these efforts aimed at emittance improvement are also given.

  10. Computer simulated plant design for waste minimization/pollution prevention

    SciTech Connect

    Bumble, S.

    2000-07-01

    The book discusses several paths to pollution prevention and waste minimization by using computer simulation programs. It explains new computer technologies used in the field of pollution prevention and waste management; provides information pertaining to overcoming technical, economic, and environmental barriers to waste reduction; gives case-studies from industries; and covers computer aided flow sheet design and analysis for nuclear fuel reprocessing.

  11. Design and numerical simulation of an optofluidic pressure sensor.

    PubMed

    Ebnali-Heidari, Majid; Mansouri, Morteza; Mokhtarian, Saeed; Moravvej-Farshi, Mohammed Kazem

    2012-06-01

    We present a numerical design procedure for an all-optical compact sensor by means of integrating the optofluidic switch polymer interferometers to measure the microfluidic air pressure and flow rate. The design is based on a flexible air gap optical cavity that can generate an interference pattern when illuminated by a monochromatic light. The optical interference pattern directly depends on the pressure. In our numerical simulations, we take the effects of fluid flow rate, solid deformation, and the light interference into account. We use the beam propagation method for simulating the optics and the finite element method for simulating the mechanics. The significance of the proposed sensor lies with its low power consumption, compactness, low cost, and short length. This sensor can operate under pressure range of 0-60±6%  Pa at a constant temperature of 20 °C. PMID:22695574

  12. ASPP2 Is a Novel Pan-Ras Nanocluster Scaffold

    PubMed Central

    Posada, Itziar M. D.; Serulla, Marc; Zhou, Yong; Oetken-Lindholm, Christina

    2016-01-01

    Ras-induced senescence mediated through ASPP2 represents a barrier to tumour formation. It is initiated by ASPP2’s interaction with Ras at the plasma membrane, which stimulates the Raf/MEK/ERK signaling cascade. Ras to Raf signalling requires Ras to be organized in nanoscale signalling complexes, called nanocluster. We therefore wanted to investigate whether ASPP2 affects Ras nanoclustering. Here we show that ASPP2 increases the nanoscale clustering of all oncogenic Ras isoforms, H-ras, K-ras and N-ras. Structure-function analysis with ASPP2 truncation mutants suggests that the nanocluster scaffolding activity of ASPP2 converges on its α-helical domain. While ASPP2 increased effector recruitment and stimulated ERK and AKT phosphorylation, it did not increase colony formation of RasG12V transformed NIH/3T3 cells. By contrast, ASPP2 was able to suppress the transformation enhancing ability of the nanocluster scaffold Gal-1, by competing with the specific effect of Gal-1 on H-rasG12V- and K-rasG12V-nanoclustering, thus imposing ASPP2’s ERK and AKT signalling signature. Similarly, ASPP2 robustly induced senescence and strongly abrogated mammosphere formation irrespective of whether it was expressed alone or together with Gal-1, which by itself showed the opposite effect in Ras wt or H-ras mutant breast cancer cells. Our results suggest that Gal-1 and ASPP2 functionally compete in nanocluster for active Ras on the plasma membrane. ASPP2 dominates the biological outcome, thus switching from a Gal-1 supported growth-promoting setting to a senescence inducing and stemness suppressive program in cancer cells. Our results support Ras nanocluster as major integrators of tumour fate decision events. PMID:27437940

  13. Design and Simulation of an Anode Stalk Support Insulator

    SciTech Connect

    Wang, L; Houck, T; Westenskow, G

    2005-05-16

    An anode stalk support insulator in a magnetically insulated transmission line was designed and modeled. One of the important design criteria is that within space constraints, the electric field along the insulator surface has to be minimized in order to prevent a surface flashover. In order to further reduce the field on the insulator surface, metal rings between insulator layers were also specially shaped. To facilitate the design process, electric field simulations were performed to determine the maximum field stress on the insulator surfaces and the transmission line chamber.

  14. Study, simulation and design of a 3D clinostat

    NASA Astrophysics Data System (ADS)

    Pavone, Valentina; Guarnieri, Vincenzo; Lobascio, Cesare; Soma, Aurelio; Bosso, Nicola; Lamantea, Matteo Maria

    High cost and limited number of physically executable experiments in space have introduced the need for ground simulation systems that enable preparing experiments to be carried out on board, identifying phenomena associated with the altered gravity conditions, and taking advantage of these conditions, as in Biotechnology. Among systems developed to simulate microgravity, especially for life sciences experiments, different types of clinostats were realized. This work deals with mechanical design of a three-dimensional clinostat and simulation of the dynamic behavior of the system by varying the operating parameters. The design and simulation phase was preceded by a careful analysis of the state of art and by the review of the most recent results, in particular from the major investigators of Life Sciences in Space. The mechanical design is quite innovative by adoption of a structure entirely in aluminum, which allows robustness while reducing the overall weight. The transmission system of motion has been optimized by means of brushless DC micro motors, light and compact, which helped to reduce weight, dimensions, power consumption and increase the reliability and durability of the system. The study of the dynamic behavior using SIMPACK, a multibody simulation software, led to results in line with those found in the most important and recent scientific publications. This model was also appropriately configured to represent any desired operating condition, and for eventual system scalability. It would be interesting to generate simulated hypogravity - e.g.: 0.38-g (Mars) or 0.17-g (Moon). This would allow to investigate how terrestrial life forms can grow in other planetary habitats, or to determine the gravity threshold response of different organisms. At the moment, such a system can only be achieved by centrifuges in real microgravity. We are confident that simulation and associated tests with our 3D clinostat can help adjusting the parameters allowing variable g

  15. Cosmic reionization on computers. I. Design and calibration of simulations

    SciTech Connect

    Gnedin, Nickolay Y.

    2014-09-20

    Cosmic Reionization On Computers is a long-term program of numerical simulations of cosmic reionization. Its goal is to model fully self-consistently (albeit not necessarily from the first principles) all relevant physics, from radiative transfer to gas dynamics and star formation, in simulation volumes of up to 100 comoving Mpc, and with spatial resolution approaching 100 pc in physical units. In this method paper, we describe our numerical method, the design of simulations, and the calibration of numerical parameters. Using several sets (ensembles) of simulations in 20 h {sup –1} Mpc and 40 h {sup –1} Mpc boxes with spatial resolution reaching 125 pc at z = 6, we are able to match the observed galaxy UV luminosity functions at all redshifts between 6 and 10, as well as obtain reasonable agreement with the observational measurements of the Gunn-Peterson optical depth at z < 6.

  16. Design of Accelerator Online Simulator Server Using Structured Data

    SciTech Connect

    Shen, Guobao; Chu, Chungming; Wu, Juhao; Kraimer, Martin; /Argonne

    2012-07-06

    Model based control plays an important role for a modern accelerator during beam commissioning, beam study, and even daily operation. With a realistic model, beam behaviour can be predicted and therefore effectively controlled. The approach used by most current high level application environments is to use a built-in simulation engine and feed a realistic model into that simulation engine. Instead of this traditional monolithic structure, a new approach using a client-server architecture is under development. An on-line simulator server is accessed via network accessible structured data. With this approach, a user can easily access multiple simulation codes. This paper describes the design, implementation, and current status of PVData, which defines the structured data, and PVAccess, which provides network access to the structured data.

  17. RAS one-equation turbulence model with non-singular eddy-viscosity coefficient

    NASA Astrophysics Data System (ADS)

    Rahman, M. M.; Agarwal, R. K.; Siikonen, T.

    2016-02-01

    A simplified consistency formulation for Pk/ε (production to dissipation ratio) is devised to obtain a non-singular Cμ (coefficient of eddy-viscosity) in the explicit algebraic Reynolds stress model of Gatski and Speziale. The coefficient Cμ depends non-linearly on both rotational/irrotational strains and is used in the framework of an improved RAS (Rahman-Agarwal-Siikonen) one-equation turbulence model to calculate a few well-documented turbulent flows, yielding predictions in good agreement with the direct numerical simulation and experimental data. The strain-dependent Cμ assists the RAS model in constructing the coefficients and functions such as to benefit complex flows with non-equilibrium turbulence. Comparisons with the Spalart-Allmaras one-equation model and the shear stress transport k-ω model demonstrate that Cμ improves the response of RAS model to non-equilibrium effects.

  18. Computational Aerodynamic Simulations of a Spacecraft Cabin Ventilation Fan Design

    NASA Technical Reports Server (NTRS)

    Tweedt, Daniel L.

    2010-01-01

    Quieter working environments for astronauts are needed if future long-duration space exploration missions are to be safe and productive. Ventilation and payload cooling fans are known to be dominant sources of noise, with the International Space Station being a good case in point. To address this issue cost effectively, early attention to fan design, selection, and installation has been recommended, leading to an effort by NASA to examine the potential for small-fan noise reduction by improving fan aerodynamic design. As a preliminary part of that effort, the aerodynamics of a cabin ventilation fan designed by Hamilton Sundstrand has been simulated using computational fluid dynamics codes, and the computed solutions analyzed to quantify various aspects of the fan aerodynamics and performance. Four simulations were performed at the design rotational speed: two at the design flow rate and two at off-design flow rates. Following a brief discussion of the computational codes, various aerodynamic- and performance-related quantities derived from the computed flow fields are presented along with relevant flow field details. The results show that the computed fan performance is in generally good agreement with stated design goals.

  19. Integrated Simulation Design Challenges to Support TPS Repair Operations

    NASA Technical Reports Server (NTRS)

    Quiocho, Leslie J.; Crues, Edwin Z.; Huynh, An; Nguyen, Hung T.; MacLean, John

    2005-01-01

    During the Orbiter Repair Maneuver (ORM) operations planned for Return to Flight (RTF), the Shuttle Remote Manipulator System (SRMS) must grapple the International Space Station (ISS), undock the Orbiter, maneuver it through a long duration trajectory, and orient it to an EVA crewman poised at the end of the Space Station Remote Manipulator System (SSRMS) to facilitate the repair of the Thermal Protection System (TPS). Once repair has been completed and confirmed, then the SRMS proceeds back through the trajectory to dock the Orbiter to the Orbiter Docking System. In order to support analysis of the complex dynamic interactions of the integrated system formed by the Orbiter, ISS, SRMS, and SSRMS during the ORM, simulation tools used for previous 'nominal' mission support required substantial enhancements. These upgrades were necessary to provide analysts with the capabilities needed to study integrated system performance. This paper discusses the simulation design challenges encountered while developing simulation capabilities to mirror the ORM operations. The paper also describes the incremental build approach that was utilized, starting with the subsystem simulation elements and integration into increasing more complex simulations until the resulting ORM worksite dynamics simulation had been assembled. Furthermore, the paper presents an overall integrated simulation V&V methodology based upon a subsystem level testing, integrated comparisons, and phased checkout.

  20. Superoxide Inhibits Guanine Nucleotide Exchange Factor (GEF) Action on Ras, but not on Rho, through Desensitization of Ras to GEF

    PubMed Central

    2015-01-01

    Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GTPases. However, the effect of oxidants on GEF functions, or vice versa, has not been known. We show that, via targeting Ras Cys51, an oxidant inhibits the catalytic action of Cdc25—the catalytic domain of RasGEFs—on Ras. However, the enhancement of Ras GNE by an oxidant continues regardless of the presence of Cdc25. Limiting RasGEF action by an oxidant may function to prevent the pathophysiological overactivation of Ras in the presence of both RasGEFs and oxidants. The continuous exposure of Ras to nitric oxide and its derivatives can form S-nitrosated Ras (Ras-SNO). This study also shows that an oxidant not only inhibits the catalytic action of Cdc25 on Ras-SNO but also fails to enhance Ras-SNO GNE. This lack of enhancement then populates the biologically inactive Ras-SNO in cells, which may function to prevent the continued redox signaling of the Ras pathophysiological response. Finally, this study also demonstrates that, unlike the case with RasGEFs, an oxidant does not inhibit the catalytic action of RhoGEF—Vav or Dbs—on Rho GTPases such as Rac1, RhoA, RhoC, and Cdc42. This result explains the results of the previous study in which, despite the presence of an oxidant, the catalytic action of Dbs in cells continued to enhance RhoC GNE. PMID:24422478

  1. Comparing simulated emission from molecular clouds using experimental design

    SciTech Connect

    Yeremi, Miayan; Flynn, Mallory; Loeppky, Jason; Rosolowsky, Erik; Offner, Stella

    2014-03-10

    We propose a new approach to comparing simulated observations that enables us to determine the significance of the underlying physical effects. We utilize the methodology of experimental design, a subfield of statistical analysis, to establish a framework for comparing simulated position-position-velocity data cubes to each other. We propose three similarity metrics based on methods described in the literature: principal component analysis, the spectral correlation function, and the Cramer multi-variate two-sample similarity statistic. Using these metrics, we intercompare a suite of mock observational data of molecular clouds generated from magnetohydrodynamic simulations with varying physical conditions. Using this framework, we show that all three metrics are sensitive to changing Mach number and temperature in the simulation sets, but cannot detect changes in magnetic field strength and initial velocity spectrum. We highlight the shortcomings of one-factor-at-a-time designs commonly used in astrophysics and propose fractional factorial designs as a means to rigorously examine the effects of changing physical properties while minimizing the investment of computational resources.

  2. Parachute system design, analysis, and simulation tool. Status report

    SciTech Connect

    Sundberg, W.D.; McBride, D.D.; Gwinn, K.W.; Waye, D.E.; Hailey, C.E.

    1992-12-31

    For over twenty years designers at Sandia National Laboratories have developed various parachute simulation codes to model deployment, inflation, loading, trajectories, aircraft downwash and line sail. In addition to these codes, material property data bases have been acquired. Recently we have initiated project to integrate these codes and data bases into a single software tool entitled SPARSYS (Sandia PARachute SYstem Simulation). We have constructed a graphical user interface as the driver and framework for SPARSYS. In this paper we present a status report on SPARSYS describing progress in developing and incorporating independent modules, in developing an integrated trajectory package, and in developing a materials data base including high-rate-of-strain data.

  3. The Differential Palmitoylation States of N-Ras and H-Ras Determine Their Distinct Golgi Sub-compartment Localizations

    PubMed Central

    Lynch, Stephen J.; Snitkin, Harriet; Gumper, Iwona; Philips, Mark R.; Sabatini, David; Pellicer, Angel

    2014-01-01

    Despite a high degree of structural homology and shared exchange factors, effectors and GTPase activating proteins, a large body of evidence suggests functional heterogeneity among Ras isoforms. One aspect of Ras biology that may explain this heterogeneity is the differential subcellular localizations driven by the C-terminal hypervariable regions of Ras proteins. Spatial heterogeneity has been documented at the level of organelles: palmitoylated Ras isoforms (H-Ras and N-Ras) localize on the Golgi apparatus whereas K-Ras4B does not. We tested the hypothesis that spatial heterogeneity also exists at the sub-organelle level by studying the localization of differentially palmitoylated Ras isoforms within the Golgi apparatus. Using confocal, live cell fluorescent imaging and immunogold electron microscopy we found that, whereas the doubly palmitoylated H-Ras is distributed throughout the Golgi stacks, the singly palmitoylated N-Ras is polarized with a relative paucity of expression on the trans Golgi. Using palmitoylation mutants we show that the different sub-Golgi distributions of the Ras proteins are a consequence of their differential degree of palmitoylation. Thus, the acylation state of Ras proteins controls not only their distribution between the Golgi apparatus and the plasma membrane but also their distribution within the Golgi stacks. PMID:25158650

  4. Simulation-Guided DNA Probe Design for Consistently Ultraspecific Hybridization

    PubMed Central

    Wang, J. Sherry; Zhang, David Yu

    2015-01-01

    Hybridization of complementary sequences is one of the central tenets of nucleic acid chemistry; however, the unintended binding of closely related sequences limits the accuracy of hybridization-based approaches for analyzing nucleic acids. Thermodynamics-guided probe design and empirical optimization of reaction conditions have been used to enable discrimination of single nucleotide variants, but typically these approaches provide only an approximate 25-fold difference in binding affinity. Here we show that simulations of the binding kinetics are both necessary and sufficient to design nucleic acid probe systems with consistently high specificity as they enable the discovery of an optimal combination of thermodynamic parameters. Simulation-guided probe systems designed against 44 different target single nucleotide variants sequences showed between 200- and 3000-fold (median 890) higher binding affinity than their corresponding wildtype sequences. As a demonstration of the usefulness of this simulation-guided design approach we developed probes which, in combination with PCR amplification, we use to detect low concentrations of variant alleles (1%) in human genomic DNA. PMID:26100802

  5. Parametric design methodology for chemical processes using a simulator

    SciTech Connect

    Diwekar, U.M.; Rubin, E.S. )

    1994-02-01

    Parameter design is a method popularized by the Japanese quality expert G. Taguchi, for designing products and manufacturing processes that are robust in the face of uncontrollable variations. At the design stage, the goal of parameter design is to identify design settings that make the product performance less sensitive to the effects of manufacturing and environmental variations and deterioration. Because parameter design reduces performance variation by reducing the influence of the sources of variation rather than by controlling them, it is a cost-effective technique for improving quality. A recent study on the application of parameter design methodology for chemical processes reported that the use of Taguchi's method was not justified and a method based on Monte Carlo simulation combined with optimization was shown to be more effective. However, this method is computationally intensive as a large number of samples are necessary to achieve the given accuracy. Additionally, determination of the number of sample runs required is based on experimentation due to a lack of systematic sampling methods. In an attempt to overcome these problems, the use of a stochastic modeling capability combined with an optimizer is presented in this paper. The objective is that of providing an effective means for application of parameter design methodologies to chemical processes using the ASPEN simulator. This implementation not only presents a generalized tool for use by chemical engineers at large but also provides systematic estimates of the number of sample runs required to attain the specified accuracy. The stochastic model employs the technique of Latin hypercube sampling instead of the traditional Monte Carlo technique and hence has a great potential to reduce the required number of samples. The methodology is illustrated via an example problem of designing a chemical process.

  6. The Design and Implementation of the Swim Integrated Plasma Simulator

    SciTech Connect

    Elwasif, Wael R; Bernholdt, David E; Shet, Aniruddha G; Foley, Samantha S; Bramley, Randall B; Batchelor, Donald B; Berry, Lee A

    2010-01-01

    As computing capabilities have increased, the coupling of computational models has become an increasingly viable and therefore important way of improving the physical fidelity of simulations. Applications currently using some form of multicode or multi-component coupling include climate modeling, rocket simulations, and chemistry. In recent years, the plasma physics community has also begun to pursue integrated multiphysics simulations for space weather and fusion energy applications. Such model coupling generally exposes new issues in the physical, mathematical, and computational aspects of the problem. This paper focuses on the computational aspects of one such effort, detailing the design, and implementation of the Integrated Plasma Simulator (IPS) for the Center for Simulation of Wave Interactions with Magnetohydrodynamics (SWIM). The IPS framework focuses on maximizing flexibility for the creators of loosely-coupled component-based simulations, and provides services for execution coordination, resource management, data management, and inter-component communication. It also serves as a proving ground for a concurrent 'multi-tasking' execution model to improve resource utilization, and application-level fault tolerance. We also briefly describe how the IPS has been applied to several problems of interest to the fusion community.

  7. Dedicated software for diffractive optics design and simulation

    NASA Astrophysics Data System (ADS)

    Firsov, A.; Brzhezinskaya, M.; Firsov, A.; Svintsov, A.; Erko, A.

    2013-03-01

    An efficient software package for the structure design and simulation of imaging properties of diffraction optical elements has been developed. It operates with point source and consists of: the ZON software, to calculate the structure of an optical element in transmission and reflection; the KRGF software, to simulate the diffraction properties of an ideal optical element with point source; the DS software, to calculate the diffraction properties by taking into consideration material and shadowing effects. Optional software allows simulation with a real non-point source. Zone plate thickness profile, source shape as well as substrate curvature are considered in this calculation. This is especially important for the diffractive focusing elements and gratings at a total external reflection, given that the lateral size of the structure can be up to 1 m. The program package can be used in combination with the Nanomaker software to prepare data for ion and e-beam surface modifications and corrections.

  8. Programmable multi-node quantum network design and simulation

    NASA Astrophysics Data System (ADS)

    Dasari, Venkat R.; Sadlier, Ronald J.; Prout, Ryan; Williams, Brian P.; Humble, Travis S.

    2016-05-01

    Software-defined networking offers a device-agnostic programmable framework to encode new network functions. Externally centralized control plane intelligence allows programmers to write network applications and to build functional network designs. OpenFlow is a key protocol widely adopted to build programmable networks because of its programmability, flexibility and ability to interconnect heterogeneous network devices. We simulate the functional topology of a multi-node quantum network that uses programmable network principles to manage quantum metadata for protocols such as teleportation, superdense coding, and quantum key distribution. We first show how the OpenFlow protocol can manage the quantum metadata needed to control the quantum channel. We then use numerical simulation to demonstrate robust programmability of a quantum switch via the OpenFlow network controller while executing an application of superdense coding. We describe the software framework implemented to carry out these simulations and we discuss near-term efforts to realize these applications.

  9. Design of 3D simulation engine for oilfield safety training

    NASA Astrophysics Data System (ADS)

    Li, Hua-Ming; Kang, Bao-Sheng

    2015-03-01

    Aiming at the demand for rapid custom development of 3D simulation system for oilfield safety training, this paper designs and implements a 3D simulation engine based on script-driven method, multi-layer structure, pre-defined entity objects and high-level tools such as scene editor, script editor, program loader. A scripting language been defined to control the system's progress, events and operating results. Training teacher can use this engine to edit 3D virtual scenes, set the properties of entity objects, define the logic script of task, and produce a 3D simulation training system without any skills of programming. Through expanding entity class, this engine can be quickly applied to other virtual training areas.

  10. Design concepts to improve high performance solar simulator

    NASA Technical Reports Server (NTRS)

    Juranek, H. J.; Frey, H. U.

    1986-01-01

    By improving several important components of the well known off-axis solar simulator system, a considerable step forward was made. The careful mathematical studies on the optics and the thermal side of the problem lead to a highly efficient system with low operational costs and a high reliability. The actual performance of the simulator is significantly better than the specified one, and the efficiency is outstanding. No more than 12 lamps operating at 18 kW are required to obtain one Solar Constant in the 6 m beam. It is now known that by using sophisticated optics, even larger facilities of high performance can be designed without leaving the proven off-axis concept and using a spherical mirror. Using high performance optics is a means of reducing costs at a given size of beam because the number of lamps is one of the most cost driving factors in the construction of a solar simulator.

  11. VINCI Altitude Simulation - Vacuum Chamber Design and Manufacturing

    NASA Astrophysics Data System (ADS)

    Delrez, C.; Collin, B.; Chisogne, J.-P.; Amestoy, S.; Hardouin, E.

    2004-08-01

    a motor driven trolley, a raising/lowering system, The purpose of this article is to describe the design, computation, production and installation of a Simplified altitude Simulation (SAS) package intended for the VINCI engine tests on the PF52bench. a duct for connection to the ejector, an engine ignition viewing system a drive and power supply assembly, a set of measuring instruments, The simulation is used to reconstitute at ground level the same flying conditions as those normally found at the altitude where the Ariane 5 launcher cryogenic engine is fired. a control and monitoring assembly. This PF52 bench, which is being modified, is located on the Snecma Moteurs Space Engine division's test site, at Vernon (France). The design, computation, production and installation of the SAS are under the responsibility of the company AMOS sa, at Angleur (Belgium).

  12. Design and Simulation of Microwave Attenuators for Superconducting Quantum Devices

    NASA Astrophysics Data System (ADS)

    Lefebvre, Jay; Yeh, Jen-Hao; Wellstood, Frederick; Palmer, Benjamin

    We have found that dephasing times for quantum superconducting transmons operating nominally at T = 20 mK can be limited by thermal photons in the read-out cavity due to non-equilibrium noise on our input microwave line. In an effort to reduce this noise, we have used finite-element simulations to design attenuators that provide better thermalization of the input microwave signals being delivered to our devices. Our thermal simulations incorporate both electron-phonon decoupling effects due to dissipated power in each element of the attenuator as well as phonon thermal conduction and Kapitza boundary effects. We combine the resulting thermal map with a thermal noise model of each dissipative element of the filter to estimate the effective noise temperature of our filter design.

  13. An automated methodology development. [software design for combat simulation

    NASA Technical Reports Server (NTRS)

    Hawley, L. R.

    1985-01-01

    The design methodology employed in testing the applicability of Ada in large-scale combat simulations is described. Ada was considered as a substitute for FORTRAN to lower life cycle costs and ease the program development efforts. An object-oriented approach was taken, which featured definitions of military targets, the capability of manipulating their condition in real-time, and one-to-one correlation between the object states and real world states. The simulation design process was automated by the problem statement language (PSL)/problem statement analyzer (PSA). The PSL/PSA system accessed the problem data base directly to enhance the code efficiency by, e.g., eliminating non-used subroutines, and provided for automated report generation, besides allowing for functional and interface descriptions. The ways in which the methodology satisfied the responsiveness, reliability, transportability, modifiability, timeliness and efficiency goals are discussed.

  14. Design and Simulation of a Valveless Micro Pump

    NASA Astrophysics Data System (ADS)

    Dau, Van Thanh; Dinh, Thien Xuan; Tanaka, Katsuhiko; Sugiyama, Susumu

    This paper reports on the design and simulation of a valveless micro pump which promises widely applicable in microfluidic applications. The structure of the pump comprises a PZT diaphragm and a fluidic network channel which can be easily fabricated by either conventional machining or silicon micromachining techniques. The working principle of the pump relies on the structure of the cross junction which connects the pump chamber, the outlet and two opposite inlet channels. This design allows a difference of fluidic resistance and momentum between the pump phases which results in a net flow from the inlet to outlet. The pump performance is studied by numerical simulation by applying the deformation of the PZT diaphragm. Experiments of the prototype had been conducted and working principle was confirmed.

  15. Simulation models and designs for advanced Fischer-Tropsch technology

    SciTech Connect

    Choi, G.N.; Kramer, S.J.; Tam, S.S.

    1995-12-31

    Process designs and economics were developed for three grass-roots indirect Fischer-Tropsch coal liquefaction facilities. A baseline and an alternate upgrading design were developed for a mine-mouth plant located in southern Illinois using Illinois No. 6 coal, and one for a mine-mouth plane located in Wyoming using Power River Basin coal. The alternate design used close-coupled ZSM-5 reactors to upgrade the vapor stream leaving the Fischer-Tropsch reactor. ASPEN process simulation models were developed for all three designs. These results have been reported previously. In this study, the ASPEN process simulation model was enhanced to improve the vapor/liquid equilibrium calculations for the products leaving the slurry bed Fischer-Tropsch reactors. This significantly improved the predictions for the alternate ZSM-5 upgrading design. Another model was developed for the Wyoming coal case using ZSM-5 upgrading of the Fischer-Tropsch reactor vapors. To date, this is the best indirect coal liquefaction case. Sensitivity studies showed that additional cost reductions are possible.

  16. Robust Multivariable Optimization and Performance Simulation for ASIC Design

    NASA Technical Reports Server (NTRS)

    DuMonthier, Jeffrey; Suarez, George

    2013-01-01

    Application-specific-integrated-circuit (ASIC) design for space applications involves multiple challenges of maximizing performance, minimizing power, and ensuring reliable operation in extreme environments. This is a complex multidimensional optimization problem, which must be solved early in the development cycle of a system due to the time required for testing and qualification severely limiting opportunities to modify and iterate. Manual design techniques, which generally involve simulation at one or a small number of corners with a very limited set of simultaneously variable parameters in order to make the problem tractable, are inefficient and not guaranteed to achieve the best possible results within the performance envelope defined by the process and environmental requirements. What is required is a means to automate design parameter variation, allow the designer to specify operational constraints and performance goals, and to analyze the results in a way that facilitates identifying the tradeoffs defining the performance envelope over the full set of process and environmental corner cases. The system developed by the Mixed Signal ASIC Group (MSAG) at the Goddard Space Flight Center is implemented as a framework of software modules, templates, and function libraries. It integrates CAD tools and a mathematical computing environment, and can be customized for new circuit designs with only a modest amount of effort as most common tasks are already encapsulated. Customization is required for simulation test benches to determine performance metrics and for cost function computation.

  17. Performance parameters in the design of flight motion simulators

    NASA Astrophysics Data System (ADS)

    Mitchell, Robert W.

    2012-06-01

    The desired test performance parameters influence the design of a Flight Motion Simulator (FMS) and affect its size, weight, power, electro-magnetic interference, noise, and vibration. A common desire is to specify requirements beyond the immediate need for future test programs. This may directly affect cost and schedule. Critical parameters that affect the FMS design are larger payload sizes, higher accuracies, and higher dynamic requirements. This paper provides a checklist of parameters and specification tradeoffs to be considered for the overall system performance requirements.

  18. Simulation Environment for Orion Launch Abort System Control Design Studies

    NASA Technical Reports Server (NTRS)

    McMinn, J. Dana; Jackson, E. Bruce; Christhilf, David M.

    2007-01-01

    The development and use of an interactive environment to perform control system design and analysis of the proposed Crew Exploration Vehicle Launch Abort System is described. The environment, built using a commercial dynamic systems design package, includes use of an open-source configuration control software tool and a collaborative wiki to coordinate between the simulation developers, control law developers and users. A method for switching between multiple candidate control laws and vehicle configurations is described. Aerodynamic models, especially in a development program, change rapidly, so a means for automating the implementation of new aerodynamic models is described.

  19. Computational studies of Ras and PI3K

    NASA Technical Reports Server (NTRS)

    Ren, Lei; Cucinotta, Francis A.

    2004-01-01

    Until recently, experimental techniques in molecular cell biology have been the primary means to investigate biological risk upon space radiation. However, computational modeling provides an alternative theoretical approach, which utilizes various computational tools to simulate proteins, nucleotides, and their interactions. In this study, we are focused on using molecular mechanics (MM) and molecular dynamics (MD) to study the mechanism of protein-protein binding and to estimate the binding free energy between proteins. Ras is a key element in a variety of cell processes, and its activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. Different computational approaches for this particular study are presented to calculate the solvation energies and binding free energies of H-Ras and PI3K. The goal of this study is to establish computational methods to investigate the roles of different proteins played in the cellular responses to space radiation, including modification of protein function through gene mutation, and to support the studies in molecular cell biology and theoretical kinetics models for our risk assessment project.

  20. Inhibition of Ras for cancer treatment: the search continues

    PubMed Central

    Baines, Antonio T.; Xu, Dapeng; Der, Channing J.

    2012-01-01

    Background The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Discussion Despite intensive effort, to date no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Conclusions Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery. PMID:22004085

  1. EGFR phosphorylates FAM129B to promote Ras activation

    PubMed Central

    Ji, Haitao; Lee, Jong-Ho; Wang, Yugang; Pang, Yilin; Zhang, Tao; Xia, Yan; Zhong, Lianjin; Lyu, Jianxin; Lu, Zhimin

    2016-01-01

    Ras GTPase-activating proteins (GAPs) are important regulators for Ras activation, which is instrumental in tumor development. However, the mechanism underlying this regulation remains elusive. We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras. FAM129B phosphorylation promoted Ras activation, increasing ERK1/2- and PKM2-dependent β-catenin transactivation and leading to the enhanced glycolytic gene expression and the Warburg effect; promoting tumor cell proliferation and invasion; and supporting brain tumorigenesis. Our studies unearthed a novel and important mechanism underlying EGFR-mediated Ras activation in tumor development. PMID:26721396

  2. Design, Fabrication, and Testing of a Hopper Spacecraft Simulator

    NASA Astrophysics Data System (ADS)

    Mucasey, Evan Phillip Krell

    A robust test bed is needed to facilitate future development of guidance, navigation, and control software for future vehicles capable of vertical takeoff and landings. Specifically, this work aims to develop both a hardware and software simulator that can be used for future flight software development for extra-planetary vehicles. To achieve the program requirements of a high thrust to weight ratio with large payload capability, the vehicle is designed to have a novel combination of electric motors and a micro jet engine is used to act as the propulsion elements. The spacecraft simulator underwent several iterations of hardware development using different materials and fabrication methods. The final design used a combination of carbon fiber and fiberglass that was cured under vacuum to serve as the frame of the vehicle which provided a strong, lightweight platform for all flight components and future payloads. The vehicle also uses an open source software development platform, Arduino, to serve as the initial flight computer and has onboard accelerometers, gyroscopes, and magnetometers to sense the vehicles attitude. To prevent instability due to noise, a polynomial kalman filter was designed and this fed the sensed angles and rates into a robust attitude controller which autonomously control the vehicle' s yaw, pitch, and roll angles. In addition to the hardware development of the vehicle itself, both a software simulation and a real time data acquisition interface was written in MATLAB/SIMULINK so that real flight data could be taken and then correlated to the simulation to prove the accuracy of the analytical model. In result, the full scale vehicle was designed and own outside of the lab environment and data showed that the software model accurately predicted the flight dynamics of the vehicle.

  3. Design & simulation of in-plane MEMS Lorentz force magnetometer

    NASA Astrophysics Data System (ADS)

    Jyoti, Aditi, Tripathi, C. C.; Gopal, Ram

    2016-03-01

    This report presents the design and simulation of a MEMS based In-plane Lorentz Force Magnetometer (I-LFM), simulated for 8 um UV-LIGA technology using FEM tool of COMSOL Multiphysics 4.3b. Designed I-LFM was simulated in the magnetic field range varied from 1 μJT to 100μJT. The proposed structure composed of a comb drive actuator, configured such that the fingers overlap with each other to generate capacitive coupling for its actuation. The magnetic field can be detected in Z-axis by this comb drive structure. The device was excited by supplying the sinusoidal current with the frequency equivalent to resonance frequency of the device at its first mode i.e. 12.047 kHz. In order to achieve the maximum mechanical output, the device was operated at the resonant frequency. Simulations based results shows a good linearity in the magnetic field range of 1 μJT to 100 μJT with a high quality factor of 130.

  4. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B.

    PubMed

    Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

    2016-01-01

    Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. In addition, we simulated 'exchanged' nucleotide states. These comprehensive simulations reveal that in solution K-Ras4B(WT)-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4B(G12C/G12D)-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID:26902995

  5. Computer simulations of realistic microstructures: Implications for simulation-based materials design

    NASA Astrophysics Data System (ADS)

    Singh, Harpreet

    The conventional route of materials development typically involves fabrication of numerous batches of specimens having a range of different microstructures generated via variations of process parameters and measurements of relevant properties of these microstructures to identify the combination of processing conditions that yield the material having desired properties. Clearly, such a trial and error based materials development methodology is expensive, time consuming, and inefficient. Consequently, it is of interest to explore alternate strategies that can lead to a decrease in the cost and time required for development of advanced materials such as composites. Availability of powerful and inexpensive computational power and progress in computational materials science permits advancement of modeling and simulations assisted materials design methodology that may require fewer experiments, and therefore, lower cost and time for materials development. The key facets of such a technology would be computational tools for (i) creating models to generate computer simulated realistic microstructures; (ii) capturing the process-microstructure relationship using these models; and (iii) implementation of simulated microstructures in the computational models for materials behavior. Therefore, development of a general and flexible methodology for simulations of realistic microstructures is crucial for the development of simulations based materials design and development technology. Accordingly, this research concerns development of such a methodology for simulations of realistic microstructures based on experimental quantitative stereological data on few microstructures that can capture relevant details of microstructural geometry (including spatial clustering and second phase particle orientations) and its variations with process parameters in terms of a set of simulation parameters. The interpolation and extrapolation of the simulation parameters can then permit generation

  6. Monte Carlo simulations for design of the KFUPM PGNAA facility

    NASA Astrophysics Data System (ADS)

    Naqvi, A. A.; Nagadi, M. M.; Khateeb-ur-Rehman; Maslehuddin, M.; Kidwai, S.

    2003-02-01

    Monte Carlo simulations were carried out to design a 2.8 MeV neutron-based prompt gamma ray neutron activation analysis (PGNAA) setup for elemental analysis of cement samples. The elemental analysis was carried out using prompt gamma rays produced through capture of thermal neutrons in sample nuclei. The basic design of the PGNAA setup consists of a cylindrical cement sample enclosed in a cylindrical high-density polyethylene moderator placed between a neutron source and a gamma ray detector. In these simulations the predominant geometrical parameters of the PGNAA setup were optimized, including moderator size, sample size and shielding of the detector. Using the results of the simulations, an experimental PGNAA setup was then fabricated at the 350 kV Accelerator Laboratory of this University. The design calculations were checked experimentally through thermal neutron flux measurements inside the PGNAA moderator. A test prompt gamma ray spectrum of the PGNAA setup was also acquired from a Portland cement sample, using a pulsed beam of 2.8 MeV neutrons. Prompt gamma ray peaks due to the calcium, silicon and iron content of the Portland cement were detected.

  7. Design and simulation of silicon photonic schematics and layouts

    NASA Astrophysics Data System (ADS)

    Chrostowski, Lukas; Lu, Zeqin; Flueckiger, Jonas; Wang, Xu; Klein, Jackson; Liu, Amy; Jhoja, Jaspreet; Pond, James

    2016-05-01

    Electronic circuit designers commonly start their design process with a schematic, namely an abstract representation of the physical circuit. In integrated photonics on the other hand, it is common for the design to begin at the physical component level, and create a layout by connecting components with interconnects. In this paper, we discuss how to create a schematic from the physical layout via netlist extraction, which enables circuit simulations. Post-layout extraction can also be used to predict how fabrication variability and non-uniformity will impact circuit performance. This is based on the component position information, compact models that are parameterized for dimensional variations, and manufacturing variability models such as a simulated wafer thickness map. This final step is critical in understanding how real-world silicon photonic circuits will behave. We present an example based on treating the ring resonator as a circuit. A silicon photonics design kit, as described here, is available for download at http://github.com/lukasc-ubc/SiEPIC_EBeam_PDK.

  8. Design and Simulation of an Electrothermal Actuator Based Rotational Drive

    NASA Astrophysics Data System (ADS)

    Beeson, Sterling; Dallas, Tim

    2008-10-01

    As a participant in the Micro and Nano Device Engineering (MANDE) Research Experience for Undergraduates program at Texas Tech University, I learned how MEMS devices operate and the limits of their operation. Using specialized AutoCAD-based design software and the ANSYS simulation program, I learned the MEMS fabrication process used at Sandia National Labs, the design limitations of this process, the abilities and drawbacks of micro devices, and finally, I redesigned a MEMS device called the Chevron Torsional Ratcheting Actuator (CTRA). Motion is achieved through electrothermal actuation. The chevron (bent-beam) actuators cause a ratcheting motion on top of a hub-less gear so that as voltage is applied the CTRA spins. The voltage applied needs to be pulsed and the frequency of the pulses determine the angular frequency of the device. The main objective was to design electromechanical structures capable of transforming the electrical signals into mechanical motion without overheating. The design was optimized using finite element analysis in ANSYS allowing multi-physics simulations of our model system.

  9. Design and Simulation of the nuSTORM Pion Beamline

    SciTech Connect

    Liu, A.; Neuffer, D.; Bross, A.

    2015-08-15

    The nuSTORM (neutrinos from STORed Muons) proposal presents a detailed design for a neutrino facility based on a muon storage ring, with muon decay in the production straight section of the ring providing well defined neutrino beams. The facility includes a primary high-energy proton beam line, a target station with pion production and collection, and a pion beamline for pion transportation and injection into a muon decay ring. The nuSTORM design uses “stochastic injection”, in which pions are directed by a chicane, referred to as the Orbit Combination Section (OCS), into the production straight section of the storage ring. Pions that decay within that straight section provide muons within the circulating acceptance of the ring. Furthermore, the design enables injection without kickers or a separate pion decay transport line. The beam line that the pions traverse before being extracted from the decay ring is referred to as the pion beamline. Our paper describes the design and simulation of the pion beamline, and includes full beam dynamics simulations of the system.

  10. Design and Simulation of the nuSTORM Pion Beamline

    DOE PAGESBeta

    Liu, A.; Neuffer, D.; Bross, A.

    2015-08-15

    The nuSTORM (neutrinos from STORed Muons) proposal presents a detailed design for a neutrino facility based on a muon storage ring, with muon decay in the production straight section of the ring providing well defined neutrino beams. The facility includes a primary high-energy proton beam line, a target station with pion production and collection, and a pion beamline for pion transportation and injection into a muon decay ring. The nuSTORM design uses “stochastic injection”, in which pions are directed by a chicane, referred to as the Orbit Combination Section (OCS), into the production straight section of the storage ring. Pionsmore » that decay within that straight section provide muons within the circulating acceptance of the ring. Furthermore, the design enables injection without kickers or a separate pion decay transport line. The beam line that the pions traverse before being extracted from the decay ring is referred to as the pion beamline. Our paper describes the design and simulation of the pion beamline, and includes full beam dynamics simulations of the system.« less

  11. Designing a Distributed Space Systems Simulation in Accordance with the Simulation Interoperability Standards Organization (SISO)

    NASA Technical Reports Server (NTRS)

    Cowen, Benjamin

    2011-01-01

    Simulations are essential for engineering design. These virtual realities provide characteristic data to scientists and engineers in order to understand the details and complications of the desired mission. A standard development simulation package known as Trick is used in developing a source code to model a component (federate in HLA terms). The runtime executive is integrated into an HLA based distributed simulation. TrickHLA is used to extend a Trick simulation for a federation execution, develop a source code for communication between federates, as well as foster data input and output. The project incorporates international cooperation along with team collaboration. Interactions among federates occur throughout the simulation, thereby relying on simulation interoperability. Communication through the semester went on between participants to figure out how to create this data exchange. The NASA intern team is designing a Lunar Rover federate and a Lunar Shuttle federate. The Lunar Rover federate supports transportation across the lunar surface and is essential for fostering interactions with other federates on the lunar surface (Lunar Shuttle, Lunar Base Supply Depot and Mobile ISRU Plant) as well as transporting materials to the desired locations. The Lunar Shuttle federate transports materials to and from lunar orbit. Materials that it takes to the supply depot include fuel and cargo necessary to continue moon-base operations. This project analyzes modeling and simulation technologies as well as simulation interoperability. Each team from participating universities will work on and engineer their own federate(s) to participate in the SISO Spring 2011 Workshop SIW Smackdown in Boston, Massachusetts. This paper will focus on the Lunar Rover federate.

  12. Design and simulation of the nuSTORM facility

    SciTech Connect

    Liu, Ao

    2015-04-01

    This thesis provides a full design and simulation of the nuSTORM beam line facility including the pion beam line , the pion and muon orbit combination section, and the muon decay ring. The study also includes the development of numerical optimization methods and their application to the design. At nuSTORM, one proton batch from the Main Injector (MI) is extracted and transported to the target station to bombard a solid target. A magnetic horn is used as the collection device for the secondary particles such as pions and kaons. A pion beam line is designed to transport the secondary particles downstream to the muon decay ring. In order to avoid the use of a fast kicker with a large aperture for the injection, an Orbit Combination Section (OCS) was designed to combine the reference pion orbit with the circulating muon orbit. This ful lls the stochastic injection scheme proposed in the 1980s. It is shown through the simulation that the pion beam line is able to deliver 0.011 muons per proton on target within the acceptance of the ring. In order to improve the circulating muon ux, an optimization of the magnetic collection horn was studied. A Multi-Objective Genetic Algorithm (MOGA), that was modi ed to integrate Message Passing Interface (MPI) in the process, is applied to the optimization. The number of muons within the ring acceptance from the pion decay is estimated by the pions after the collection horn. This new method was proposed to lower the requirement on the computing resources for the optimization. The study gives a new and better target and horn con guration after a full investigation of the system. The nuSTORM ring is examined with two optics designs. With di erent features, the two designs are optimized via correcting the nonlinearities with sextupolar eld distribution in the ring. A modi ed MPI-based Simulated Annealing (SA) algorithm was applied to obtain the optimal ring acceptance. The comparison with the GA shows good agreements on the achieved

  13. Guiding without feeling guided: Implicit scaffolding through interactive simulation design

    NASA Astrophysics Data System (ADS)

    Paul, Ariel; Podolefsky, Noah; Perkins, Katherine

    2013-01-01

    While PhET interactive simulations (sims) were historically designed for college students, they are used at lower grade levels, and we are currently developing sims targeted at middle school (MS). In studying how MS students interact with and learn from these sims, we have been extracting insights about design for the middle-grade-levels and across K-16. This collection of work has highlighted the importance of implicit scaffolding, a design framework that reduces the amount of explicit instruction needed to facilitate learning. We present a case study of redesigning a sim - Energy Skate Park (ESP) - for effective use in MS. We conducted think-aloud interviews with MS students to identify successful features, sources of confusion or unproductive distraction, as well as features inconsistent with gradeappropriate learning goals. Drawing on these data and the principle of implicit scaffolding, we developed Energy Skate Park Basics (ESPB). Interviews on ESPB demonstrate increased usability and learning for MS students.

  14. RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally

    PubMed Central

    Miller, Mark Steven; Miller, Lance D.

    2012-01-01

    Mutation in RAS proteins is one of the most common genetic alterations observed in human and experimentally induced rodent cancers. In vivo, oncogenic mutations have been shown to occur at exons 12, 13, and 61, resulting in any 1 of 19 possible point mutations in a given tumor for a specific RAS isoform. While some studies have suggested a possible role of different mutant alleles in determining tumor severity and phenotype, no general consensus has emerged on the oncogenicity of different mutant alleles in tumor formation and progression. Part of this may be due to a lack of a single, signature pathway that shows significant alterations between different mutations. Rather, it is likely that subtle differences in the activation, or lack thereof, of downstream effectors by different RAS mutant alleles may determine the eventual outcome in terms of tumor phenotype. This paper reviews our current understanding of the potential role of different RAS mutations on tumorigenesis, highlights studies in model cell culture and in vivo systems, and discusses the potential of expression array and computational network modeling to dissect out differences in activated RAS genes in conferring a transforming phenotype. PMID:22303394

  15. Ras Family Small GTPase-mediated Neuroprotective Signaling in Stroke

    PubMed Central

    Shi, Geng-Xian; Andres, Douglas A.; Cai, Weikang

    2012-01-01

    Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of stroke, the overall mechanisms governing the balance between cell survival and death are not well-defined. Ras family small GTPases are activated following ischemic insults, and in turn, serve as intrinsic switches to regulate neuronal survival and regeneration. Their ability to integrate diverse intracellular signal transduction pathways makes them critical regulators and potential therapeutic targets for neuronal recovery after stroke. This article highlights the contribution of Ras family GTPases to neuroprotective signaling cascades, including mitogen-activated protein kinase (MAPK) family protein kinase- and AKT/PKB-dependent signaling pathways as well as the regulation of cAMP response element binding (CREB), Forkhead box O (FoxO) and hypoxia-inducible factor 1(HIF1) transcription factors, in stroke. PMID:21521171

  16. Designing laboratory wind simulations using artificial neural networks

    NASA Astrophysics Data System (ADS)

    Križan, Josip; Gašparac, Goran; Kozmar, Hrvoje; Antonić, Oleg; Grisogono, Branko

    2015-05-01

    While experiments in boundary layer wind tunnels remain to be a major research tool in wind engineering and environmental aerodynamics, designing the modeling hardware required for a proper atmospheric boundary layer (ABL) simulation can be costly and time consuming. Hence, possibilities are sought to speed-up this process and make it more time-efficient. In this study, two artificial neural networks (ANNs) are developed to determine an optimal design of the Counihan hardware, i.e., castellated barrier wall, vortex generators, and surface roughness, in order to simulate the ABL flow developing above urban, suburban, and rural terrains, as previous ANN models were created for one terrain type only. A standard procedure is used in developing those two ANNs in order to further enhance best-practice possibilities rather than to improve existing ANN designing methodology. In total, experimental results obtained using 23 different hardware setups are used when creating ANNs. In those tests, basic barrier height, barrier castellation height, spacing density, and height of surface roughness elements are the parameters that were varied to create satisfactory ABL simulations. The first ANN was used for the estimation of mean wind velocity, turbulent Reynolds stress, turbulence intensity, and length scales, while the second one was used for the estimation of the power spectral density of velocity fluctuations. This extensive set of studied flow and turbulence parameters is unmatched in comparison to the previous relevant studies, as it includes here turbulence intensity and power spectral density of velocity fluctuations in all three directions, as well as the Reynolds stress profiles and turbulence length scales. Modeling results agree well with experiments for all terrain types, particularly in the lower ABL within the height range of the most engineering structures, while exhibiting sensitivity to abrupt changes and data scattering in profiles of wind-tunnel results. The

  17. Design, modeling, simulation and evaluation of a distributed energy system

    NASA Astrophysics Data System (ADS)

    Cultura, Ambrosio B., II

    This dissertation presents the design, modeling, simulation and evaluation of distributed energy resources (DER) consisting of photovoltaics (PV), wind turbines, batteries, a PEM fuel cell and supercapacitors. The distributed energy resources installed at UMass Lowell consist of the following: 2.5kW PV, 44kWhr lead acid batteries and 1500W, 500W & 300W wind turbines, which were installed before year 2000. Recently added to that are the following: 10.56 kW PV array, 2.4 kW wind turbine, 29 kWhr Lead acid batteries, a 1.2 kW PEM fuel cell and 4-140F supercapacitors. Each newly added energy resource has been designed, modeled, simulated and evaluated before its integration into the existing PV/Wind grid-connected system. The Mathematical and Simulink model of each system was derived and validated by comparing the simulated and experimental results. The Simulated results of energy generated from a 10.56kW PV system are in good agreement with the experimental results. A detailed electrical model of a 2.4kW wind turbine system equipped with a permanent magnet generator, diode rectifier, boost converter and inverter is presented. The analysis of the results demonstrates the effectiveness of the constructed simulink model, and can be used to predict the performance of the wind turbine. It was observed that a PEM fuel cell has a very fast response to load changes. Moreover, the model has validated the actual operation of the PEM fuel cell, showing that the simulated results in Matlab Simulink are consistent with the experimental results. The equivalent mathematical equation, derived from an electrical model of the supercapacitor, is used to simulate its voltage response. The model is completely capable of simulating its voltage behavior, and can predict the charge time and discharge time of voltages on the supercapacitor. The bi-directional dc-dc converter was designed in order to connect the 48V battery bank storage to the 24V battery bank storage. This connection was

  18. An approximate simulation model for initial luge track design.

    PubMed

    Mössner, Martin; Hasler, Michael; Schindelwig, Kurt; Kaps, Peter; Nachbauer, Werner

    2011-03-15

    Competitive and recreational sport on artificial ice tracks has grown in popularity. For track design one needs knowledge of the expected speed and acceleration of the luge on the ice track. The purpose of this study was to develop an approximate simulation model for luge in order to support the initial design of new ice tracks. Forces considered were weight, drag, friction, and surface reaction force. The trajectory of the luge on the ice track was estimated using a quasi-static force balance and a 1d equation of motion was solved along that trajectory. The drag area and the coefficient of friction for two runs were determined by parameter identification using split times of five sections of the Whistler Olympic ice track. The values obtained agreed with experimental data from ice friction and wind tunnel measurements. To validate the ability of the model to predict speed and accelerations normal to the track surface, a luge was equipped with an accelerometer to record the normal acceleration during the entire run. Simulated and measured normal accelerations agreed well. In a parameter study the vertical drop and the individual turn radii turned out to be the main variables that determine speed and acceleration. Thus the safety of a new ice track is mainly ensured in the planning phase, in which the use of a simulation model similar to this is essential. PMID:21185562

  19. High-Density Plasma Reactors: Simulations for Design

    NASA Technical Reports Server (NTRS)

    Hash, David B.; Meyyappan, Meyya; Arnold, James O. (Technical Monitor)

    1998-01-01

    The development of improved and more efficient plasma reactors is a costly process for the semiconductor industry. Until five years ago, the Industry made most of its advancements through a trial and error approach. More recently, the role of computational modeling in the design process has increased. Both conventional computational fluid dynamics (CFD) techniques like Navier-Stokes solvers as well as particle simulation methods are used to model plasma reactor flowfields. However, since high-density plasma reactors generally operate at low gas pressures on the order of 1 to 10 mTorr, a particle simulation may be necessary because of the failure of CFD techniques to model rarefaction effects. The direct simulation Monte Carlo method is the most widely accepted and employed particle simulation tool and has previously been used to investigate plasma reactor flowfields. A plasma DSMC code is currently under development at NASA Ames Research Center with its foundation as the object-oriented parallel Cornell DSMC code, MONACO. The present investigation is a follow up of a neutral flow investigation of the effects of process parameters as well as reactor design on etch rate and etch rate uniformity. The previous work concentrated on silicon etch of a chlorine flow in a configuration typical of electron cyclotron resonance (ECR) or helical resonator type reactors. The effects of the plasma on the dissociation chemistry were modeled by making assumptions about the electron temperature and number density. The electrons or ions themselves were not simulated.The present work extends these results by simulating the charged species.The electromagnetic fields are calculated such that power deposition is modeled self-consistently. Electron impact reactions are modeled along with mechanisms for charge exchange. An bipolar diffusion assumption is made whereby electrons remain tied to the ions. However, the velocities of tile electrons are allowed to be modified during collisions

  20. R-Ras contributes to LTP and contextual discrimination.

    PubMed

    Darcy, M J; Jin, S-X; Feig, L A

    2014-09-26

    The ability to discriminate between closely related contexts is a specific form of hippocampal-dependent learning that may be impaired in certain neurodegenerative disorders such as Alzheimer's and Down Syndrome. However, signaling pathways regulating this form of learning are poorly understood. Previous studies have shown that the calcium-dependent exchange factor Ras-GRF1, an activator of Rac, Ras and R-Ras GTPases, is important for this form of learning and memory. Moreover, the ability to discriminate contexts was linked to the ability of Ras-GRF1 to promote high-frequency stimulation long-term potentiation (HFS-LTP) via the activation of p38 Map kinase. Here, we show that R-Ras is involved in this form of learning by using virally-delivered miRNAs targeting R-Ras into the CA1 region of the dorsal hippocampus and observing impaired contextual discrimination. Like the loss of GRF1, knockdown of R-Ras in the CA1 also impairs the induction of HFS-LTP and p38 Map kinase. Nevertheless, experiments indicate that this involvement of R-Ras in HFS-LTP that is required for contextual discrimination is independent of Ras-GRF1. Thus, R-Ras is a novel regulator of a form of hippocampal-dependent LTP as well as learning and memory that is affected in certain forms of neurodegenerative diseases. PMID:25043327

  1. Autophagic activity dictates the cellular response to oncogenic RAS

    PubMed Central

    Wang, Yihua; Wang, Xiao Dan; Lapi, Eleonora; Sullivan, Alexandra; Jia, Wei; He, You-Wen; Ratnayaka, Indrika; Zhong, Shan; Goldin, Robert D.; Goemans, Christoph G.; Tolkovsky, Aviva M.; Lu, Xin

    2012-01-01

    RAS is frequently mutated in human cancers and has opposing effects on autophagy and tumorigenesis. Identifying determinants of the cellular responses to RAS is therefore vital in cancer research. Here, we show that autophagic activity dictates the cellular response to oncogenic RAS. N-terminal Apoptosis-stimulating of p53 protein 2 (ASPP2) mediates RAS-induced senescence and inhibits autophagy. Oncogenic RAS-expressing ASPP2(Δ3/Δ3) mouse embryonic fibroblasts that escape senescence express a high level of ATG5/ATG12. Consistent with the notion that autophagy levels control the cellular response to oncogenic RAS, overexpressing ATG5, but not autophagy-deficient ATG5 mutant K130R, bypasses RAS-induced senescence, whereas ATG5 or ATG3 deficiency predisposes to it. Mechanistically, ASPP2 inhibits RAS-induced autophagy by competing with ATG16 to bind ATG5/ATG12 and preventing ATG16/ATG5/ATG12 formation. Hence, ASPP2 modulates oncogenic RAS-induced autophagic activity to dictate the cellular response to RAS: to proliferate or senesce. PMID:22847423

  2. Co-Simulation for Advanced Process Design and Optimization

    SciTech Connect

    Stephen E. Zitney

    2009-01-01

    Meeting the increasing demand for clean, affordable, and secure energy is arguably the most important challenge facing the world today. Fossil fuels can play a central role in a portfolio of carbon-neutral energy options provided CO{sub 2} emissions can be dramatically reduced by capturing CO{sub 2} and storing it safely and effectively. Fossil energy industry faces the challenge of meeting aggressive design goals for next-generation power plants with CCS. Process designs will involve large, highly-integrated, and multipurpose systems with advanced equipment items with complex geometries and multiphysics. APECS is enabling software to facilitate effective integration, solution, and analysis of high-fidelity process/equipment (CFD) co-simulations. APECS helps to optimize fluid flow and related phenomena that impact overall power plant performance. APECS offers many advanced capabilities including ROMs, design optimization, parallel execution, stochastic analysis, and virtual plant co-simulations. NETL and its collaborative R&D partners are using APECS to reduce the time, cost, and technical risk of developing high-efficiency, zero-emission power plants with CCS.

  3. Design and verification of a cloud field optical simulator

    NASA Technical Reports Server (NTRS)

    Davis, J. M.; Cox, S. K.; Mckee, T. B.

    1982-01-01

    A concept and an apparatus designed to investigate the reflected and transmitted distributions of light from optically thick clouds is presented. The Cloud Field Optical Simulator (CFOS) is a laboratory device which utilizes an array of incandescent lamps as a source, simulated clouds made from cotton or styrofoam as targets, and an array of silicon photodiodes as detectors. The device allows virtually any source-target-detector geometry to be examined. Similitude between real clouds and their CFOS cotton or styrofoam counterparts is established by relying on a linear relationship between optical depth and the ratio of reflected to transmitted light for a semi-infinite layer. Comparisons of principal plane radiances observed by the CFOS with Monte Carlo computations for a water cloud at 0.7 microns show excellent agreement.

  4. Design and verification of a cloud field optical simulator

    NASA Technical Reports Server (NTRS)

    Davis, J. M.; Cox, S. K.; Mckee, T. B.

    1983-01-01

    A concept and an apparatus designed to investigate the reflected and transmitted distributions of light from optically thick clouds is presented. The Cloud Field Optical Simulator (CFOS) is a laboratory device which utilizes an array of incandescent lamps as a source, simulated clouds made from cotton or styrofoam as targets, and an array of silicon photodiodes as detectors. The device allows virtually any source-target-detector geometry to be examined. Similitude between real clouds and their CFOS cotton or styrofoam counterparts is established by relying on a linear relationship between optical depth and the ratio of reflected to transmitted light for a semiinfinite layer. Comparisons of principal plane radiances observed by the CFOS with Monte Carlo computations for a water cloud at 0.7 micron show excellent agreement. Initial applications of the CFOS are discussed.

  5. Design of virtual SCADA simulation system for pressurized water reactor

    NASA Astrophysics Data System (ADS)

    Wijaksono, Umar; Abdullah, Ade Gafar; Hakim, Dadang Lukman

    2016-02-01

    The Virtual SCADA system is a software-based Human-Machine Interface that can visualize the process of a plant. This paper described the results of the virtual SCADA system design that aims to recognize the principle of the Nuclear Power Plant type Pressurized Water Reactor. This simulation uses technical data of the Nuclear Power Plant Unit Olkiluoto 3 in Finland. This device was developed using Wonderware Intouch, which is equipped with manual books for each component, animation links, alarm systems, real time and historical trending, and security system. The results showed that in general this device can demonstrate clearly the principles of energy flow and energy conversion processes in Pressurized Water Reactors. This virtual SCADA simulation system can be used as instructional media to recognize the principle of Pressurized Water Reactor.

  6. Design and simulation of uncooled microbolometer using coventorware

    NASA Astrophysics Data System (ADS)

    Arora, Suryansh; Paras, Neha; Gurjar, Anil; Narwal, Rakesh; Prasad, B.; Kumar, Dinesh

    2016-04-01

    Recently, a lot of attention has been paid to infrared imaging using uncooled microbolometer detectors, primarily because of their low cost, and wide military and civilian applications like disaster rescue, night vision, homing and tracking, ecology and weather forecasting, target acquisition, predictive inspection and maintenance, surveillance, remote temperature sensing and medical diagnostic and treatment. The present work demonstrates the design and simulation of uncooled microbolometer detector using Coventorware tool. Geometrical optimization has been done to minimize the pixel size up to 18×18 µm. Simulated values for Different parameters like Thermal conductance, Time constant and change in temperature calculated for the structure are 1.2 × 10-7W/K, 4.44ms and 3.5K.

  7. Effects of an Experiential Learning Simulation Design on Clinical Nursing Judgment Development.

    PubMed

    Chmil, Joyce Victor; Turk, Melanie; Adamson, Katie; Larew, Charles

    2015-01-01

    Simulation design should be theory based and its effect on outcomes evaluated. This study (1) applied a model of experiential learning to design a simulation experience, (2) examined how this design affected clinical nursing judgment development, and (3) described the relationship between clinical nursing judgment development and student performance when using the experiential learning design. Findings suggest that using an experiential learning simulation design results in more highly developed nursing judgment and competency in simulation performance. PMID:25763781

  8. Differential involvement of Ras-GRF1 and Ras-GRF2 in L-DOPA-induced dyskinesia

    PubMed Central

    Bido, Simone; Solari, Nicola; Indrigo, Marzia; D’Antoni, Angela; Brambilla, Riccardo; Morari, Michele; Fasano, Stefania

    2015-01-01

    Objective Recent findings have shown that pharmacogenetic manipulations of the Ras-ERK pathway provide a therapeutic means to tackle l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID). First, we investigated whether a prolonged l-DOPA treatment differentially affected ERK signaling in medium spiny neurons of the direct pathway (dMSNs) and in cholinergic aspiny interneurons (ChIs) and assessed the role of Ras-GRF1 in both subpopulations. Second, using viral-assisted technology, we probed Ras-GRF1 and Ras-GRF2 as potential targets in this pathway. We investigated how selective blockade of striatal Ras-GRF1 or Ras-GRF2 expression impacted on LID (induction, maintenance, and reversion) and its neurochemical correlates. Methods We used both Ras-GRF1 knockout mice and lentiviral vectors (LVs) delivering short-hairpin RNA sequences (shRNAs) to obtain striatum-specific gene knockdown of Ras-GRF1 and Ras-GRF2. The consequences of these genetic manipulations were evaluated in the 6-hydroxydopamine mouse model of Parkinson’s disease. Escalating doses of l-DOPA were administered and then behavioral analysis with immunohistochemical assays and in vivo microdialysis were performed. Results Ras-GRF1 was found essential in controlling ERK signaling in dMSNs, but its ablation did not prevent ERK activation in ChIs. Moreover, striatal injection of LV-shRNA/Ras-GRF1 attenuated dyskinesia development and ERK-dependent signaling, whereas LV-shRNA/Ras-GRF2 was without effect, ruling out the involvement of Ras-GRF2 in LID expression. Accordingly, Ras-GRF1 but not Ras-GRF2 striatal gene-knockdown reduced l-DOPA-induced GABA and glutamate release in the substantia nigra pars reticulata, a neurochemical correlate of dyskinesia. Finally, inactivation of Ras-GRF1 provided a prolonged anti-dyskinetic effect for up to 7 weeks and significantly attenuated symptoms in animals with established LID. Interpretation Our results suggest that Ras-GRF1 is a promising target for LID

  9. Beam Dynamics Design and Simulation in Ion Linear Accelerators (

    Energy Science and Technology Software Center (ESTSC)

    2006-08-01

    Orginally, the ray tracing code TRACK has been developed to fulfill the many special requirements for the Rare Isotope Accelerator Facility known as RIA. Since no available beam-dynamics code met all the necessary requirements, modifications to the code TRACK were introduced to allow end-to-end (from the ion souce to the production target) simulations of the RIA machine, TRACK is a general beam-dynamics code and can be applied for the design, commissioning and operation of modernmore » ion linear accelerators and beam transport systems.« less

  10. Beam Dynamics Design and Simulation in Ion Linear Accelerators (

    SciTech Connect

    Ostroumov, Peter N.; Asseev, Vladislav N.; Mustapha, and Brahim

    2006-08-01

    Orginally, the ray tracing code TRACK has been developed to fulfill the many special requirements for the Rare Isotope Accelerator Facility known as RIA. Since no available beam-dynamics code met all the necessary requirements, modifications to the code TRACK were introduced to allow end-to-end (from the ion souce to the production target) simulations of the RIA machine, TRACK is a general beam-dynamics code and can be applied for the design, commissioning and operation of modern ion linear accelerators and beam transport systems.